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'''''Chlamydia felis''''' (formerly ''Chlamydophila felis'' and before that ''Chlamydia psittaci'' var. ''felis'') is a bacterium [[Endemic (epidemiology)|endemic]] among [[domestic cat]]s worldwide, primarily causing inflammation of feline conjunctiva, rhinitis and respiratory problems. ''C. felis'' can be recovered from the stomach and reproductive tract. [[Zoonosis|Zoonotic infection]] of humans with ''C. felis'' has been reported. Strains FP Pring and FP Cello have an extrachromosomal plasmid, whereas the FP Baker strain does not. FP Cello produces lethal disease in mice, whereas the FP Baker does not. An attenuated FP Baker strain, and an attenuated 905 strain, are used as live vaccines for cats.
'''''Chlamydia felis''''' (formerly ''Chlamydophila felis'' and before that ''Chlamydia psittaci'' var. ''felis'') is a [[Gram-negative bacteria|Gram-negative]], [[Intracellular parasite|obligate intracellular]] [[Pathogenic bacteria|bacterial pathogen]] that infects cats.<ref name=":13">{{Cite journal|last=Azuma|first=Yoshinao|last2=Hirakawa|first2=Hideki|last3=Yamashita|first3=Atsushi|last4=Cai|first4=Yan|last5=Rahman|first5=Mohd Akhlakur|last6=Suzuki|first6=Harumi|last7=Mitaku|first7=Shigeki|last8=Toh|first8=Hidehiro|last9=Goto|first9=Susumu|last10=Murakami|first10=Tomoyuki|last11=Sugi|first11=Kazuro|date=2006-01-01|title=Genome Sequence of the Cat Pathogen, Chlamydophila felis|url=https://academic.oup.com/dnaresearch/article/13/1/15/486747|journal=DNA Research|language=en|volume=13|issue=1|pages=15–23|doi=10.1093/dnares/dsi027|issn=1340-2838}}</ref> It is [[Endemic (epidemiology)|endemic]] among [[domestic cat]]s worldwide, primarily causing inflammation of feline conjunctiva, rhinitis and respiratory problems. ''C. felis'' can be recovered from the stomach and reproductive tract. [[Zoonosis|Zoonotic infection]] of humans with ''C. felis'' has been reported. Strains FP Pring and FP Cello have an extrachromosomal plasmid, whereas the FP Baker strain does not. FP Cello produces lethal disease in mice, whereas the FP Baker does not. An attenuated FP Baker strain, and an attenuated 905 strain, are used as live vaccines for cats.


== Taxonomy and Phylogeny ==
==Genome structure==
The genus ''[[Chlamydia]]'' contains the species ''[[Chlamydia trachomatis|C. trachomatis]], [[Chlamydia psittaci|C. psittaci]], [[Chlamydia abortus|C. abortus]], C. felis, [[Chlamydia muridarum|C. muridarum]], [[Chlamydia suis|C. suis]], [[Chlamydia caviae|C. caviae]], [[Chlamydia pecorum|C. pecorum]],'' and ''[[Chlamydia pneumoniae|C. pneumoniae]].''<ref name=":92">{{Citation|last=Fox|first=James G.|title=Chapter 28 - Selected Zoonoses|date=2015-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780124095274000286|work=Laboratory Animal Medicine (Third Edition)|pages=1313–1370|editor-last=Fox|editor-first=James G.|series=American College of Laboratory Animal Medicine|publisher=Academic Press|language=en|isbn=978-0-12-409527-4|access-date=2020-04-24|last2=Otto|first2=Glen|last3=Colby|first3=Lesley A.|editor2-last=Anderson|editor2-first=Lynn C.|editor3-last=Otto|editor3-first=Glen M.|editor4-last=Pritchett-Corning|editor4-first=Kathleen R.}}</ref> However, there is some dispute that some of these species, including ''C. felis'', should be classified in a separate genus, ''[[Chlamydophila]]'', but this has not been widely accepted.<ref name=":92" /> ''C. felis'' is closely related to ''C. pneumoniae'' (causes [[pneumonia]] in humans)'', C. trachomatis'' (causes [[Chlamydia]] in humans), and ''C. muridarum'' (causes pneumonia in mice).<ref name=":13" /> ''C. pneumoniae'' shares 879 [[orthologs]], [[Gene|genes]] that come from a common ancestor, with ''C. felis'' while ''C. trachomatis'' and ''C. muridarium'' both share 841 orthologs with ''C.felis''.<ref name=":13" /> All ''Chlamydia'' species are [[Gram-negative bacteria|Gram-negative]], [[Intracellular pathogens|obligate intracellular pathogens]] with two distinct life stages (see Characterization) that are able to infect a wide range of mammals and birds around the world.<ref name=":92" /><ref name=":13" />
''C. felis'' has relatively small genome that contains 1.17 Mbp with 1,005 protein coding genes. Additionally, it carries 7,5 kbp long [[plasmid]].<ref>{{Cite journal | last1 = Azuma | first1 = Y. | last2 = Hirakawa | first2 = H. | last3 = Yamashita | first3 = A. | last4 = Cai | first4 = Y. | last5 = Rahman | first5 = MA. | last6 = Suzuki | first6 = H. | last7 = Mitaku | first7 = S. | last8 = Toh | first8 = H. | last9 = Goto | first9 = S. | last10 = Murakami | first10 = T. | last11 = Sugi | first11 = K. | last12 = Hayashi | first12 = H. | last13 = Fukushi | first13 = H. | last14 = Hattori | first14 = M. | last15 = Kuhara | first15 = S. | last16 = Shirai | first16 = M. | title = Genome sequence of the cat pathogen, Chlamydophila felis | journal = DNA Res | volume = 13 | issue = 1 | pages = 15–23 |date=Feb 2006 | doi = 10.1093/dnares/dsi027 | pmid = 16766509 | display-authors = 8 | doi-access = free }}</ref>

== Discovery ==
James A. Baker published the finding of ''Chlamydia felis'' (known as ''Chlamydophila felis'' at the time) in 1942, but did not classify the organism.<ref name=":82">{{Cite journal|last=Baker|first=James A.|date=1942-11-20|title=A Virus Obtained from a Pneumonia of Cats and Its Possible Relation to the Cause of Atypical Pneumonia in Man|url=https://science.sciencemag.org/content/96/2499/475|journal=Science|language=en|volume=96|issue=2499|pages=475–476|doi=10.1126/science.96.2499.475|issn=0036-8075|pmid=17743467}}</ref> The organism was not formally classified until 1999.<ref>{{Cite journal|last=Everett|first=Karin D. E.|last2=Bush|first2=Robin M.|last3=Andersen|first3=Arthur A.|date=1999|title=Emended description of the order Chlamydiales, proposal of Parachlamydiaceae fam. nov. and Simkaniaceae fam. nov., each containing one monotypic genus, revised taxonomy of the family Chlamydiaceae, including a new genus and five new species, and standards for the identification of organisms|url=https://www.microbiologyresearch.org/content/journal/ijsem/10.1099/00207713-49-2-415|journal=International Journal of Systematic and Evolutionary Microbiology,|volume=49|issue=2|pages=415–440|doi=10.1099/00207713-49-2-415|issn=1466-5026}}</ref> Baker started researching ''C. felis'' due to the number of atypical [[pneumonia]] cases observed in cats and later discovered that the atypical human pneumonia cases coincided with feline cases.<ref name=":82" /> Cats infected with this atypical pneumonia were recognized by their symptoms of sneezing, coughing, and [[ocular]] and [[Nasal cavity|nasal]] discharge.<ref name=":82" /> The disease was characterized by its highly infectious nature and long infection time.<ref name=":82" /> To determine what the causative agent was, Baker made a suspension of the infected cat lungs and used the suspension to infect mice via their nasal passage.<ref name=":82" /> He also infected fertilized egg yolks.<ref name=":82" /> The infected specimens died 2-5 days after initial infection depending on what method and conditions Baker used to infect the organisms.<ref name=":82" /> After [[autopsy]] of the deceased specimens, Baker confirmed that they died from the same disease from the condition of the lungs of the mice.<ref name=":82" /> However, Baker could not culture ''C. felis'' using the available culturing methods of the time<ref name=":82" /> He tried a wide variety of different media but saw little bacterial growth<ref name=":82" /> Thus, Baker thought that the causative agent might be a [[virus]], but received more confusing results when using the [[Berkefeld filter|Berkefeld filters]].<ref name=":82" /> Baker did find the causative agent when he spun the infected mouse lungs in a [[centrifuge]].<ref name=":82" /> He found the elementary bodies (see Characterization sub-heading) of ''C. felis'' that had been separated from the mouse lungs, confirming that they were the causative agent of the disease.<ref name=":82" />

== Characterization ==
''C. felis'' is a [[Gram-negative bacteria|Gram negative]] (also known as [[Diderms|diderm]]),<ref>{{Cite journal|last=Otten|first=Christian|last2=Brilli|first2=Matteo|last3=Vollmer|first3=Waldemar|last4=Viollier|first4=Patrick H.|last5=Salje|first5=Jeanne|date=2018|title=Peptidoglycan in obligate intracellular bacteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/mmi.13880|journal=Molecular Microbiology|language=en|volume=107|issue=2|pages=142–163|doi=10.1111/mmi.13880|issn=1365-2958|pmc=PMC5814848|pmid=29178391}}</ref> [[Microaerophile|microaerophilic]]<ref name=":22">{{Cite journal|last=Omsland|first=Anders|last2=Sixt|first2=Barbara Susanne|last3=Horn|first3=Matthias|last4=Hackstadt|first4=Ted|date=2014-07-01|title=Chlamydial metabolism revisited: interspecies metabolic variability and developmental stage-specific physiologic activities|url=https://academic.oup.com/femsre/article/38/4/779/758958|journal=FEMS Microbiology Reviews|language=en|volume=38|issue=4|pages=779–801|doi=10.1111/1574-6976.12059|issn=0168-6445}}</ref> [[Bacteria|bacterium]], whose cell wall seems to lack [[peptidoglycan]].<ref name=":02">{{Cite web|title=Chlamydia felis {{!}}|url=http://www.abcdcatsvets.org/chlamydia-chlamydophila-felis/|language=en-GB|access-date=2020-04-04}}</ref> It's [[Morphology (biology)|morphology]] is that of a [[coccobacillus]].<ref name=":02" /> ''C. felis'' is also an [[Intracellular parasite|obligate intracellular pathogen]] that infects [[Eukaryote|eukaryotic]] cells, specifically cats, but has [[Zoonosis|zoonotic]] potential.<ref name=":13" /> The [[Bacteria|bacterium]] like many in its [[phylum]], has evolved to have two distinct life stages: the elementary body (EB) and the reticulate body (RB).<ref name=":22" /> The EB is the infectious phase of the pathogen and is characterized by reduced [[Metabolism|metabolic]] activity and the inability to replicate.<ref name=":22" /> The exact morphology of the EB varies among species within the ''[[Chlamydiae]]'' phylum.<ref name=":22" /> On the other hand, the RB is the replicative phase of the pathogen's life cycle and has a higher metabolic activity compared to the EB.<ref name=":22" /> When the extracellular phase (EB) infects the host eukaryotic cell via [[endocytosis]] the bacteria transforms into the replicative phase (RB) while remaining in a membrane-bound [[Vesicle (biology and chemistry)|vesicle]] called an inclusion.<ref name=":22" /> Within the inclusion the RB cells will avoid the host cell's defenses, such as [[Lysosome|lysosomes]], grow, and divide by [[Fission (biology)|binary fission]].<ref name=":22" /> This method of infection and replication is common among the ''[[Chlamydia (genus)|Chlamydia]]'' genus. However, it is currently unknown how the bacteria receive their nutrients from the host while residing in the inclusion.<ref name=":22" />

=== Metabolism ===
Many [[Metabolism|metabolic]] processes and genes are highly conserved among ''[[Chlamydia]]''.<ref name=":22" /><ref name=":13" /> Due to ''C. felis''<nowiki/>'s, and ''Chlamydia'' in general, small [[genome]], it is missing the genes for several essential [[Enzyme|enzymes]] for metabolic pathways, such as [[glycolysis]] and the [[citric acid cycle]].<ref name=":22" /> It cannot synthesize [[Nucleotide|nucleotides]], nor many [[Cofactor (biochemistry)|cofactors]] or [[Amino acid|amino acids]].<ref name=":22" /> However, the [[Bacteria|bacteria's]] ability to synthesize and/or scavenge amino acids and nucleotides varies from species-to-species and from strain-to-strain, as shown by ''C. felis's'' ability to synthesize the [[tryptophan]].<ref name=":22" /><ref name=":13" /> In order to survive, ''C. felis'' will take various [[Metabolite|metabolites]], such as [[Phosphorylation|phosphorylated]] sugars, and other essential molecules from the host cell.<ref name=":22" /> It is currently unknown exactly how the bacteria receive these molecules while residing in the inclusion.<ref name=":22" /> However, it is thought that the bacteria receive host [[Lipid|lipids]] by intercepting [[Vesicle (biology and chemistry)|vesicles]] departing from the [[Golgi apparatus]] and by stealing lipid droplets and host lipid [[Protein|transfer proteins]].<ref name=":22" /> With the nutrients gathered from the host cell, the bacteria can perform [[glycolysis]] and the [[citric acid cycle]].<ref name=":22" /> The bacteria also have a fully functional [[electron transport chain]] (ETC), which includes a Na<sup>+</sup> translocating [[NADH dehydrogenase (quinone)|NADH dehydrogenase]], [[cytochrome bd oxidase]], and a [[V-ATPase|V-type ATPase]].<ref name=":22" /> ''C. felis'' uses oxygen as it's terminal [[electron acceptor]], in which the cytochrome bd oxidase is necessary.<ref name=":22" /> The presence of a Na<sup>+</sup> translocating NADH dehydrogenase suggests that instead of a [[Proton-motive force|proton motive force]], the bacteria uses a sodium motive force for creating an [[electrochemical gradient]] across the [[Cell membrane|plasma membrane]].<ref name=":22" /> ''C. felis'' has also been shown to have a complete [[pentose phosphate pathway]] (PPP) and [[gluconeogenesis]] pathway, as well as being capable of both creating and degrading [[glycogen]].<ref name=":22" />

=== Genome ===
In order to sequence the genome, a bacterial culture was needed. The culture was obtained by inoculating fertilized chicken eggs with a ''C. felis'' strain collected from [[Conjunctiva|conjunctival]] mucus of an infected cat.<ref name=":13" /> After the strain had gone through several chicken egg passages, the strain went through four passages of McCoy cells before finally being used for genetic analysis.<ref name=":13" /> The genome of ''C. felis'' was sequenced via [[Shotgun sequencing|whole genome shotgun]].<ref name=":13" /> Each gene was then annotated by programs [[BLAST (biotechnology)|BLASTP]] and [[FASTA]].<ref name=":13" /> Programs GenomeGambler, GeneHacker plus, and Glimmer 2.0 were used to predict protein-coding genes.<ref name=":13" /> To search from [[Transmembrane protein|transmembrane proteins]], the program [[SOSUI]] was used, and tRNAscan-SE for [[Transfer RNA|tRNA genes]].<ref name=":13" /> ''C. felis'' has one [[circular chromosome]] that consists of around 1,100,00 [[Base pair|base pairs]].<ref name=":13" /> Compared to non-pathogenic organisms, the size of the ''C. felis'' is relatively small.<ref name=":22" /> The [[Gene|genes]] that ''C. felis'' does possess encode over 1,000 proteins.<ref name=":13" /> Many of the genes are highly conserved within the ''[[Chlamydia]]'' genus.<ref name=":13" /> A specific [[plasmid]] is also highly conserved among ''Chlamydia''.<ref name=":13" /> The plasmid ''C. felis'' possess is called pCfe1 and is about 7,500 base pairs long.<ref name=":13" /> A recent study has suggested that the plasmid is necessary for [[Pathogen|pathogenicity]], though the exact mechanism is currently unknown.<ref>{{Cite journal|last=Zhong|first=Guangming|date=2017-02-01|title=Chlamydial Plasmid-Dependent Pathogenicity|url=http://www.sciencedirect.com/science/article/pii/S0966842X1630138X|journal=Trends in Microbiology|language=en|volume=25|issue=2|pages=141–152|doi=10.1016/j.tim.2016.09.006|issn=0966-842X}}</ref>

=== Ecology ===
''C. felis'' was originally discovered in the lungs of cats suffering from pneumonia.<ref name=":82" /> Although ''C. felis'' was not classified as a unique species at the time, it was attributed with being the disease causing agent within the cats.<ref name=":82" /> ''C. felis'' used to be considered a strain of another member of its [[genus]], ''[[Chlamydia psittaci|C. psittaci]]'' until it was recognized as a separate [[species]] and reclassified as ''Chlamydophila felis''.<ref name=":13" /> ''Chlamydophila felis'' was then reclassified to ''Chlamydia felis'' due to dispute on the taxonomic usage of ''[[Chlamydophila]]'', which is still disputed to this day.<ref name=":92" /> As stated in the characterization section, ''C. felis'' is an [[Intracellular parasite|obligate intracellular pathogen]] that mainly infects [[Cat|cats]].<ref name=":13" /> Like other members of it's [[genus]], ''C. felis'' is a pathogen found worldwide.<ref name=":10">{{Cite web|title=Feline Chlamydiosis|url=https://www.zoetis.co.uk/conditions/cats/feline-chlamydiosis2.aspx|website=www.zoetis.co.uk|language=en|access-date=2020-05-07}}</ref> ''C. felis'' has been reported to infect humans as well, giving it [[Zoonosis|zoonotic]] potential, though it is rare.<ref name=":10" /> Humans that are infected can suffer from conjunctivitis and/or respiratory problems.<ref name=":5">{{Cite journal|last=Halánová|first=Monika|last2=Petrová|first2=Lenka|last3=Halán|first3=Miloš|last4=Trbolová|first4=Alexandra|last5=Babinská|first5=Ingrid|last6=Weissová|first6=Tatiana|date=2019-06-17|title=Impact of way of life and environment on the prevalence of Chlamydia felis in cats as potentional sources of infection for humans|url=http://www.aaem.pl/Impact-of-way-of-life-and-environment-on-the-prevalence-of-Chlamydia-felis-in-cats,100655,0,2.html|journal=Annals of Agricultural and Environmental Medicine|language=english|volume=26|issue=2|pages=222–226|doi=10.26444/aaem/100655|issn=1232-1966}}</ref> As typical of many members of its genus, ''C. felis'' is well adapted to live within its host (cats for ''C. felis'') and cannot survive for long outside of the host.<ref name=":11">{{Cite web|title=Chlamydophila felis infection (feline chlamydophilosis) {{!}} International Cat Care|url=https://icatcare.org/advice/chlamydophila-felis-infection-feline-chlamydophilosis/|website=icatcare.org|access-date=2020-05-07}}</ref> Thus, direct contact is necessary for the pathogen to spread and is why ''C. felis'' infection is more common in multi-cat environments.<ref name=":11" />

==== Disease ====
Infected cats typically contract [[conjunctivitis]] within a 2-5 day incubation period.<ref name=":3">{{Cite journal|last=Marti|first=Iris|last2=Pisano|first2=Simone R. R.|last3=Wehrle|first3=Martin|last4=Meli|first4=Marina L.|last5=Hofmann-Lehmann|first5=Regina|last6=Ryser-Degiorgis|first6=Marie-Pierre|date=2019/04|title=Severe Conjunctivitis Associated with Chlamydia felis Infection in a Free-ranging Eurasian Lynx (Lynx lynx)|url=https://bioone.org/journals/Journal-of-Wildlife-Diseases/volume-55/issue-2/2018-05-142/Severe-Conjunctivitis-Associated-with-Chlamydia-felis-Infection-in-a-Free/10.7589/2018-05-142.full|journal=Journal of Wildlife Diseases|volume=55|issue=2|pages=522–525|doi=10.7589/2018-05-142|issn=0090-3558}}</ref> Clinical signs of infection are [[hyperaemia]] of the [[nictitating membrane]] (severity varies), [[blepharospasm]], and discharge from the eye.<ref name=":02" /><ref name=":3" /><ref name=":4">{{Cite journal|last=Gruffydd-Jones|first=Tim|last2=Addie|first2=Diane|last3=Belák|first3=Sándor|last4=Boucraut-Baralon|first4=Corine|last5=Egberink|first5=Herman|last6=Frymus|first6=Tadeusz|last7=Hartmann|first7=Katrin|last8=Hosie|first8=Margaret J|last9=Lloret|first9=Albert|last10=Lutz|first10=Hans|last11=Marsilio|first11=Fulvio|date=2009-07|title=Chlamydophila Felis Infection: ABCD Guidelines on Prevention and Management|url=https://journals.sagepub.com/doi/10.1016/j.jfms.2009.05.009|journal=Journal of Feline Medicine and Surgery|language=en-US|volume=11|issue=7|pages=605–609|doi=10.1016/j.jfms.2009.05.009|issn=1098-612X}}</ref> The infection is not deadly, but if left untreated may cause blindness and pain for the cat.<ref name=":6">{{Cite web|title=Blindness {{!}} International Cat Care|url=https://icatcare.org/advice/blindness/|website=icatcare.org|access-date=2020-04-04}}</ref> Infection is commonly spread among cats by [[Eye|ocular]] secretion.<ref name=":02" /> ''C. felis'' infection is most common in multicat environments such as shelters, breeder [[Cattery|catteries]], and among stray cat communities.<ref name=":02" /> Young cats, around the age of one year or under, are at the highest risk of infection.<ref name=":02" /> Infection can be detected either by culturing a sample or by [[Polymerase chain reaction|PCR]].<ref name=":02" /> Ocular samples are the most common, but samples can also be [[Pharynx|oropharyngeal]], nasal, and/or oral.<ref name=":02" /> The infection can be treated with [[Antibiotic|antibiotics]], typically with [[Tetracycline antibiotics|tetracyclines]].<ref name=":02" /> [[Vaccine|Vaccines]] for ''C. felis'', both [[Attenuated vaccine|attenuated]] and [[Inactivated vaccine|inactivated]], are available for cats.<ref name=":02" /> For [[Immunodeficiency|immunocompromised]] cats it is recommended that they only receive the inactivated vaccine, and only if necessary.<ref name=":02" />

== Significance ==

=== Zoonotic Potential ===
''C. felis'' typically has low [[Zoonosis|zoonotic]] potential which is the likelihood that a [[pathogen]] can be spread from animal to human and still cause disease.<ref name=":5" /> People who own or handle cats regularly are at a higher risk of contracting an infection from an afflicted cat.<ref name=":5" /> The risk is even higher if the individual is [[Immunodeficiency|immunocompromised]] or if there is poor hygiene.<ref name=":5" /> In humans, ''C. felis'' could cause [[conjunctivitis]], various respiratory problems, and other diseases.<ref name=":5" /> Since most human cases are [[asymptomatic]], it is possible that this zoonosis occurs more often than we know.<ref name=":5" />

=== Cat Health ===
''C. felis'' is a common cause of [[conjunctivitis]] and [[Upper respiratory tract infection|upper respiratory problems]] in cats.<ref name=":6" /> If left untreated, it leads to damage in the eyes followed by a loss of vision and, eventually, [[blindness]].<ref name=":6" /> While this is not fatal, it is still very uncomfortable for the cat.<ref name=":6" /> However, many countries do have a [[vaccine]] available.<ref name=":5" />

=== Adoption ===
Up to 95% of cats with this infection come from shelters that have poor hygiene practices.<ref name=":5" /> The presence of other animals, like in an animal shelter, increases prevalence.<ref name=":5" /> ''C felis'' relies on contact with other animals to spread.<ref name=":5" /> This could have an impact on the adoption rates of animals in infected shelters.<ref name=":7">{{Cite thesis|title=Factors affecting the welfare and adoption rate of cats in an animal shelter|url=https://open.library.ubc.ca/cIRcle/collections/ubctheses/831/items/1.0090034|publisher=University of British Columbia|date=2001|first=Nadine|last=Gourkow}}</ref> People generally prefer cats that appear happy, healthy, and playful.<ref name=":7" /> However, some cats are adopted out of pity.<ref name=":7" />

=== Economic Impact ===
''C. felis'' has been isolated from up to 30% of cats with [[conjunctivitis]] or [[Upper respiratory tract infection|upper respiratory tract disease]].<ref>{{Cite journal|last=Wons|first=Juliana|last2=Meiller|first2=Ralph|last3=Bergua|first3=Antonio|last4=Bogdan|first4=Christian|last5=Geißdörfer|first5=Walter|date=2017|title=Follicular Conjunctivitis due to Chlamydia felis—Case Report, Review of the Literature and Improved Molecular Diagnostics|url=https://www.frontiersin.org/articles/10.3389/fmed.2017.00105/full|journal=Frontiers in Medicine|language=English|volume=4|doi=10.3389/fmed.2017.00105|issn=2296-858X}}</ref> [[Doxycycline|Doxycyline]] is an [[antibiotic]] that is commonly used to treat these infections at a dosage of 10 mg/kg of body weight daily for four weeks.<ref name=":4" /> One 100 mg [[Capsule (pharmacy)|capsule]] can cost anywhere from $0.61 to $13.26 USD.<ref>{{Cite web|title=Doxycycline|url=https://www.drugbank.ca/drugs/DB00254|website=www.drugbank.ca|access-date=2020-04-12}}</ref> This cost of treatment can be financially limiting considering that all cats within a facility, shelter, or home must be treated regardless of whether they are infected to ensure the disease is effectively eradicated.<ref name=":4" />


==See also==
==See also==

Revision as of 00:53, 23 May 2020

Chlamydia felis
Scientific classification Edit this classification
Domain: Bacteria
Phylum: Chlamydiota
Class: Chlamydiia
Order: Chlamydiales
Family: Chlamydiaceae
Genus: Chlamydia
Species:
C. felis
Binomial name
Chlamydia felis
Everett et al., 1999[1]

Chlamydia felis (formerly Chlamydophila felis and before that Chlamydia psittaci var. felis) is a Gram-negative, obligate intracellular bacterial pathogen that infects cats.[2] It is endemic among domestic cats worldwide, primarily causing inflammation of feline conjunctiva, rhinitis and respiratory problems. C. felis can be recovered from the stomach and reproductive tract. Zoonotic infection of humans with C. felis has been reported. Strains FP Pring and FP Cello have an extrachromosomal plasmid, whereas the FP Baker strain does not. FP Cello produces lethal disease in mice, whereas the FP Baker does not. An attenuated FP Baker strain, and an attenuated 905 strain, are used as live vaccines for cats.

Taxonomy and Phylogeny

The genus Chlamydia contains the species C. trachomatis, C. psittaci, C. abortus, C. felis, C. muridarum, C. suis, C. caviae, C. pecorum, and C. pneumoniae.[3] However, there is some dispute that some of these species, including C. felis, should be classified in a separate genus, Chlamydophila, but this has not been widely accepted.[3] C. felis is closely related to C. pneumoniae (causes pneumonia in humans), C. trachomatis (causes Chlamydia in humans), and C. muridarum (causes pneumonia in mice).[2] C. pneumoniae shares 879 orthologs, genes that come from a common ancestor, with C. felis while C. trachomatis and C. muridarium both share 841 orthologs with C.felis.[2] All Chlamydia species are Gram-negative, obligate intracellular pathogens with two distinct life stages (see Characterization) that are able to infect a wide range of mammals and birds around the world.[3][2]

Discovery

James A. Baker published the finding of Chlamydia felis (known as Chlamydophila felis at the time) in 1942, but did not classify the organism.[4] The organism was not formally classified until 1999.[5] Baker started researching C. felis due to the number of atypical pneumonia cases observed in cats and later discovered that the atypical human pneumonia cases coincided with feline cases.[4] Cats infected with this atypical pneumonia were recognized by their symptoms of sneezing, coughing, and ocular and nasal discharge.[4] The disease was characterized by its highly infectious nature and long infection time.[4] To determine what the causative agent was, Baker made a suspension of the infected cat lungs and used the suspension to infect mice via their nasal passage.[4] He also infected fertilized egg yolks.[4] The infected specimens died 2-5 days after initial infection depending on what method and conditions Baker used to infect the organisms.[4] After autopsy of the deceased specimens, Baker confirmed that they died from the same disease from the condition of the lungs of the mice.[4] However, Baker could not culture C. felis using the available culturing methods of the time[4] He tried a wide variety of different media but saw little bacterial growth[4] Thus, Baker thought that the causative agent might be a virus, but received more confusing results when using the Berkefeld filters.[4] Baker did find the causative agent when he spun the infected mouse lungs in a centrifuge.[4] He found the elementary bodies (see Characterization sub-heading) of C. felis that had been separated from the mouse lungs, confirming that they were the causative agent of the disease.[4]

Characterization

C. felis is a Gram negative (also known as diderm),[6] microaerophilic[7] bacterium, whose cell wall seems to lack peptidoglycan.[8] It's morphology is that of a coccobacillus.[8] C. felis is also an obligate intracellular pathogen that infects eukaryotic cells, specifically cats, but has zoonotic potential.[2] The bacterium like many in its phylum, has evolved to have two distinct life stages: the elementary body (EB) and the reticulate body (RB).[7] The EB is the infectious phase of the pathogen and is characterized by reduced metabolic activity and the inability to replicate.[7] The exact morphology of the EB varies among species within the Chlamydiae phylum.[7] On the other hand, the RB is the replicative phase of the pathogen's life cycle and has a higher metabolic activity compared to the EB.[7] When the extracellular phase (EB) infects the host eukaryotic cell via endocytosis the bacteria transforms into the replicative phase (RB) while remaining in a membrane-bound vesicle called an inclusion.[7] Within the inclusion the RB cells will avoid the host cell's defenses, such as lysosomes, grow, and divide by binary fission.[7] This method of infection and replication is common among the Chlamydia genus. However, it is currently unknown how the bacteria receive their nutrients from the host while residing in the inclusion.[7]

Metabolism

Many metabolic processes and genes are highly conserved among Chlamydia.[7][2] Due to C. felis's, and Chlamydia in general, small genome, it is missing the genes for several essential enzymes for metabolic pathways, such as glycolysis and the citric acid cycle.[7] It cannot synthesize nucleotides, nor many cofactors or amino acids.[7] However, the bacteria's ability to synthesize and/or scavenge amino acids and nucleotides varies from species-to-species and from strain-to-strain, as shown by C. felis's ability to synthesize the tryptophan.[7][2] In order to survive, C. felis will take various metabolites, such as phosphorylated sugars, and other essential molecules from the host cell.[7] It is currently unknown exactly how the bacteria receive these molecules while residing in the inclusion.[7] However, it is thought that the bacteria receive host lipids by intercepting vesicles departing from the Golgi apparatus and by stealing lipid droplets and host lipid transfer proteins.[7] With the nutrients gathered from the host cell, the bacteria can perform glycolysis and the citric acid cycle.[7] The bacteria also have a fully functional electron transport chain (ETC), which includes a Na+ translocating NADH dehydrogenase, cytochrome bd oxidase, and a V-type ATPase.[7] C. felis uses oxygen as it's terminal electron acceptor, in which the cytochrome bd oxidase is necessary.[7] The presence of a Na+ translocating NADH dehydrogenase suggests that instead of a proton motive force, the bacteria uses a sodium motive force for creating an electrochemical gradient across the plasma membrane.[7] C. felis has also been shown to have a complete pentose phosphate pathway (PPP) and gluconeogenesis pathway, as well as being capable of both creating and degrading glycogen.[7]

Genome

In order to sequence the genome, a bacterial culture was needed. The culture was obtained by inoculating fertilized chicken eggs with a C. felis strain collected from conjunctival mucus of an infected cat.[2] After the strain had gone through several chicken egg passages, the strain went through four passages of McCoy cells before finally being used for genetic analysis.[2] The genome of C. felis was sequenced via whole genome shotgun.[2] Each gene was then annotated by programs BLASTP and FASTA.[2] Programs GenomeGambler, GeneHacker plus, and Glimmer 2.0 were used to predict protein-coding genes.[2] To search from transmembrane proteins, the program SOSUI was used, and tRNAscan-SE for tRNA genes.[2] C. felis has one circular chromosome that consists of around 1,100,00 base pairs.[2] Compared to non-pathogenic organisms, the size of the C. felis is relatively small.[7] The genes that C. felis does possess encode over 1,000 proteins.[2] Many of the genes are highly conserved within the Chlamydia genus.[2] A specific plasmid is also highly conserved among Chlamydia.[2] The plasmid C. felis possess is called pCfe1 and is about 7,500 base pairs long.[2] A recent study has suggested that the plasmid is necessary for pathogenicity, though the exact mechanism is currently unknown.[9]

Ecology

C. felis was originally discovered in the lungs of cats suffering from pneumonia.[4] Although C. felis was not classified as a unique species at the time, it was attributed with being the disease causing agent within the cats.[4] C. felis used to be considered a strain of another member of its genus, C. psittaci until it was recognized as a separate species and reclassified as Chlamydophila felis.[2] Chlamydophila felis was then reclassified to Chlamydia felis due to dispute on the taxonomic usage of Chlamydophila, which is still disputed to this day.[3] As stated in the characterization section, C. felis is an obligate intracellular pathogen that mainly infects cats.[2] Like other members of it's genus, C. felis is a pathogen found worldwide.[10] C. felis has been reported to infect humans as well, giving it zoonotic potential, though it is rare.[10] Humans that are infected can suffer from conjunctivitis and/or respiratory problems.[11] As typical of many members of its genus, C. felis is well adapted to live within its host (cats for C. felis) and cannot survive for long outside of the host.[12] Thus, direct contact is necessary for the pathogen to spread and is why C. felis infection is more common in multi-cat environments.[12]

Disease

Infected cats typically contract conjunctivitis within a 2-5 day incubation period.[13] Clinical signs of infection are hyperaemia of the nictitating membrane (severity varies), blepharospasm, and discharge from the eye.[8][13][14] The infection is not deadly, but if left untreated may cause blindness and pain for the cat.[15] Infection is commonly spread among cats by ocular secretion.[8] C. felis infection is most common in multicat environments such as shelters, breeder catteries, and among stray cat communities.[8] Young cats, around the age of one year or under, are at the highest risk of infection.[8] Infection can be detected either by culturing a sample or by PCR.[8] Ocular samples are the most common, but samples can also be oropharyngeal, nasal, and/or oral.[8] The infection can be treated with antibiotics, typically with tetracyclines.[8] Vaccines for C. felis, both attenuated and inactivated, are available for cats.[8] For immunocompromised cats it is recommended that they only receive the inactivated vaccine, and only if necessary.[8]

Significance

Zoonotic Potential

C. felis typically has low zoonotic potential which is the likelihood that a pathogen can be spread from animal to human and still cause disease.[11] People who own or handle cats regularly are at a higher risk of contracting an infection from an afflicted cat.[11] The risk is even higher if the individual is immunocompromised or if there is poor hygiene.[11] In humans, C. felis could cause conjunctivitis, various respiratory problems, and other diseases.[11] Since most human cases are asymptomatic, it is possible that this zoonosis occurs more often than we know.[11]

Cat Health

C. felis is a common cause of conjunctivitis and upper respiratory problems in cats.[15] If left untreated, it leads to damage in the eyes followed by a loss of vision and, eventually, blindness.[15] While this is not fatal, it is still very uncomfortable for the cat.[15] However, many countries do have a vaccine available.[11]

Adoption

Up to 95% of cats with this infection come from shelters that have poor hygiene practices.[11] The presence of other animals, like in an animal shelter, increases prevalence.[11] C felis relies on contact with other animals to spread.[11] This could have an impact on the adoption rates of animals in infected shelters.[16] People generally prefer cats that appear happy, healthy, and playful.[16] However, some cats are adopted out of pity.[16]

Economic Impact

C. felis has been isolated from up to 30% of cats with conjunctivitis or upper respiratory tract disease.[17] Doxycyline is an antibiotic that is commonly used to treat these infections at a dosage of 10 mg/kg of body weight daily for four weeks.[14] One 100 mg capsule can cost anywhere from $0.61 to $13.26 USD.[18] This cost of treatment can be financially limiting considering that all cats within a facility, shelter, or home must be treated regardless of whether they are infected to ensure the disease is effectively eradicated.[14]

See also

References

  1. ^ Everett, K. D. E.; Bush, R. M.; Andersen, A. A. (1999). "Emended description of the order Chlamydiales, proposal of Parachlamydiaceae fam. nov. and Simkaniaceae fam. nov., each containing one monotypic genus, revised taxonomy of the family Chlamydiaceae, including a new genus and five new species, and standards for the identification of organisms". International Journal of Systematic Bacteriology. 49 (2): 415–440. doi:10.1099/00207713-49-2-415. ISSN 0020-7713. PMID 10319462.
  2. ^ a b c d e f g h i j k l m n o p q r s t Azuma, Yoshinao; Hirakawa, Hideki; Yamashita, Atsushi; Cai, Yan; Rahman, Mohd Akhlakur; Suzuki, Harumi; Mitaku, Shigeki; Toh, Hidehiro; Goto, Susumu; Murakami, Tomoyuki; Sugi, Kazuro (2006-01-01). "Genome Sequence of the Cat Pathogen, Chlamydophila felis". DNA Research. 13 (1): 15–23. doi:10.1093/dnares/dsi027. ISSN 1340-2838.
  3. ^ a b c d Fox, James G.; Otto, Glen; Colby, Lesley A. (2015-01-01), Fox, James G.; Anderson, Lynn C.; Otto, Glen M.; Pritchett-Corning, Kathleen R. (eds.), "Chapter 28 - Selected Zoonoses", Laboratory Animal Medicine (Third Edition), American College of Laboratory Animal Medicine, Academic Press, pp. 1313–1370, ISBN 978-0-12-409527-4, retrieved 2020-04-24
  4. ^ a b c d e f g h i j k l m n o Baker, James A. (1942-11-20). "A Virus Obtained from a Pneumonia of Cats and Its Possible Relation to the Cause of Atypical Pneumonia in Man". Science. 96 (2499): 475–476. doi:10.1126/science.96.2499.475. ISSN 0036-8075. PMID 17743467.
  5. ^ Everett, Karin D. E.; Bush, Robin M.; Andersen, Arthur A. (1999). "Emended description of the order Chlamydiales, proposal of Parachlamydiaceae fam. nov. and Simkaniaceae fam. nov., each containing one monotypic genus, revised taxonomy of the family Chlamydiaceae, including a new genus and five new species, and standards for the identification of organisms". International Journal of Systematic and Evolutionary Microbiology,. 49 (2): 415–440. doi:10.1099/00207713-49-2-415. ISSN 1466-5026.{{cite journal}}: CS1 maint: extra punctuation (link)
  6. ^ Otten, Christian; Brilli, Matteo; Vollmer, Waldemar; Viollier, Patrick H.; Salje, Jeanne (2018). "Peptidoglycan in obligate intracellular bacteria". Molecular Microbiology. 107 (2): 142–163. doi:10.1111/mmi.13880. ISSN 1365-2958. PMC 5814848. PMID 29178391.{{cite journal}}: CS1 maint: PMC format (link)
  7. ^ a b c d e f g h i j k l m n o p q r s t u Omsland, Anders; Sixt, Barbara Susanne; Horn, Matthias; Hackstadt, Ted (2014-07-01). "Chlamydial metabolism revisited: interspecies metabolic variability and developmental stage-specific physiologic activities". FEMS Microbiology Reviews. 38 (4): 779–801. doi:10.1111/1574-6976.12059. ISSN 0168-6445.
  8. ^ a b c d e f g h i j k "Chlamydia felis |". Retrieved 2020-04-04.
  9. ^ Zhong, Guangming (2017-02-01). "Chlamydial Plasmid-Dependent Pathogenicity". Trends in Microbiology. 25 (2): 141–152. doi:10.1016/j.tim.2016.09.006. ISSN 0966-842X.
  10. ^ a b "Feline Chlamydiosis". www.zoetis.co.uk. Retrieved 2020-05-07.
  11. ^ a b c d e f g h i j Halánová, Monika; Petrová, Lenka; Halán, Miloš; Trbolová, Alexandra; Babinská, Ingrid; Weissová, Tatiana (2019-06-17). "Impact of way of life and environment on the prevalence of Chlamydia felis in cats as potentional sources of infection for humans". Annals of Agricultural and Environmental Medicine. 26 (2): 222–226. doi:10.26444/aaem/100655. ISSN 1232-1966.
  12. ^ a b "Chlamydophila felis infection (feline chlamydophilosis) | International Cat Care". icatcare.org. Retrieved 2020-05-07.
  13. ^ a b Marti, Iris; Pisano, Simone R. R.; Wehrle, Martin; Meli, Marina L.; Hofmann-Lehmann, Regina; Ryser-Degiorgis, Marie-Pierre (2019/04). "Severe Conjunctivitis Associated with Chlamydia felis Infection in a Free-ranging Eurasian Lynx (Lynx lynx)". Journal of Wildlife Diseases. 55 (2): 522–525. doi:10.7589/2018-05-142. ISSN 0090-3558. {{cite journal}}: Check date values in: |date= (help)
  14. ^ a b c Gruffydd-Jones, Tim; Addie, Diane; Belák, Sándor; Boucraut-Baralon, Corine; Egberink, Herman; Frymus, Tadeusz; Hartmann, Katrin; Hosie, Margaret J; Lloret, Albert; Lutz, Hans; Marsilio, Fulvio (2009-07). "Chlamydophila Felis Infection: ABCD Guidelines on Prevention and Management". Journal of Feline Medicine and Surgery. 11 (7): 605–609. doi:10.1016/j.jfms.2009.05.009. ISSN 1098-612X. {{cite journal}}: Check date values in: |date= (help)
  15. ^ a b c d "Blindness | International Cat Care". icatcare.org. Retrieved 2020-04-04.
  16. ^ a b c Gourkow, Nadine (2001). Factors affecting the welfare and adoption rate of cats in an animal shelter (Thesis). University of British Columbia.
  17. ^ Wons, Juliana; Meiller, Ralph; Bergua, Antonio; Bogdan, Christian; Geißdörfer, Walter (2017). "Follicular Conjunctivitis due to Chlamydia felis—Case Report, Review of the Literature and Improved Molecular Diagnostics". Frontiers in Medicine. 4. doi:10.3389/fmed.2017.00105. ISSN 2296-858X.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  18. ^ "Doxycycline". www.drugbank.ca. Retrieved 2020-04-12.

Further reading

  • Hillström, Anna; Tvedten, Harold; Källberg, Maria; Hanås, Sofia; Lindhe, Anna; Holst, Bodil Ström (2012). "Evaluation of cytologic findings in feline conjunctivitis". Veterinary Clinical Pathology. 41 (2): 283–290. doi:10.1111/j.1939-165X.2012.00423.x. PMID 22551068.
  • Halanova, Monika; Sulinova, Zlatana; Cislakova, L; Trbolova, A; Palenik, L; Weissova, T; Halan, M; Kalinova, Z; Holickova, M (November 2011). "Chlamydophila felis in Cats - Are the Stray Cats Dangerous Source of Infection?". Zoonoses and Public Health. 58 (7): 519–522. doi:10.1111/j.1863-2378.2011.01397.x. PMID 21824351.