Discussion of Two Studies of Candida auris

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Discussionof Two Studies of Candidaauris

Discussionof Two Studies of Candidaauris

Hospital-basedinfections complicate the process of treating diseases. Candidaauris(C.auris)is a fungal pathogen that is widely known for its capacity to causehospital-based infections. It is a multidrug resistant agent thatinfects human being. It is associated with the mortality rate of 66 %and treatment failure (Chattterjee, Alampalli, Nageshan, Chettiar,Joshi &amp Tatu, 2015). It is also associated with bloodstream andwound infection. This paper provides a discussion of two studies ofCandidaauris.

Thefindings of the first study, which was conducted by, by Chattterjee,Alampalli, Nageshan, Chettiar, Joshi &amp Tatu (2015) indicated thatCandidaaurishas a divergent relationship with other members of the species. Thelevel of alignment in their genome sequence is about 0.5 % only. Inother words, 99.5 % of the genome sequence of C.aurisdoes match with that of other pathogens, including C.lusitaniae, C. albicans, Saccharomyces cerevisiae, and C. glabrata.However, C.aurisshares a lot of similarities with other Candida pathogens in terms ofvirulence. Some of the key attributes of virulence that are shared bythese pathogens include the presence of oligopeptides, mannosyltransferase, transporters, and proteases that take part in theformation of biofilm. Therefore, the lack of similarity in genomesequence should be used in differential diagnosis for C.auris. Theauthors identified that the difficulty of distinguishing C. aurisfrom other Candida species is attributed to their biochemicalsimilarities and the lack of molecular biomarkers. They also foundout that the differences in the genetic sequence of Candida speciesis directly correlated with their respective methods of reproduction.Most importantly, the study findings showed that the gene that codesfor the mating factor α is unique to each species. The genome of themajor Candida pathogens (such as C. albicans, and C. auris) was foundto have common transcription factors, such as MADS-box andSTE-related proteins. These transcription factors are associated withvirulence of plant and human fungal pathogens, respectively. Theauthors also found out that the capacity of C. auris to acquirenutrient versatility and adapt to different environments isattributed by the presence of oligopeptides that code for OPTproteins.

Differentmethods were used to evaluate the similarity in genome sequence forC.aurisand other species of Candida. The first method involved the isolationof pathogens from patients, where Yeast Peptone Dextrose was used asthe major reagent. This was followed by the use of growth assays andminimum inhibitory concentrations to assess the in vivosusceptibility of the pathogens to anti-fungal drugs. The keyreagents used in this method include broth, micro-dilutions, and YPDbroth. The third method involved the determination of the genomesequence of the pathogens, which was followed by the analysis of thequalities of genome reads using the Genotype proprietary tool.Reagents that are used in this step include enzymes, ligate adaptors,MinElute column and agarose gel. The next method was theelectrophoretic karyotyping of C.albicansand C.auris,which was accomplished using yeast and YPD medium. The other methodwas the construction of phylogenetic tree and the determination ofevolutionary analysis. The next method involved the comparison ofgenome that was sequenced in the previous steps, which was done usingBiostrings of Bioconductor and CGD. This was supported by polymerasechain reaction that was done through the isolation of genomic DNA.The last method involved the ploidy analysis, which was done usingFACS. Reagents used in this method include YPD broth, sodiumphosphate dibasic, ethanol, potassium phosphate monobasicRNAse A, andprodium iodine.

Thereis no major controversy in the article. However, the findingsindicate that 99.5 % of genome of C. auris is different from otherpathogens. This contradicts the initial assertion made in thebackground section of the article that C.aurisis often misidentified in the clinical settings.

Thefindings of the second study, which was conducted by Sherry, Ramage,Kean, Borman, Johnson, Richardson &amp Rautemaa-Richardson (2017)indicated that Candida species cause death among hospitalizedpatients through the formation of biofilms. Surprisingly, the studyfindings showed that C.aurishas the capacity to resist caspofugin, in spite of the fact that ithas been shown to be effective against the biofilms produced by otherCandida species. This resistance is the major cause of high virulenceof C.aurisand its ability to survive the hospital environment. The highvirulence and resistance associated with C.aurisimplies that the use of anti-fungal to maintain hygiene cannot leadto effective prevention of hospital-based infections. Therefore, theauthors found out that the hospital-based infection can be preventedthrough the use of anti-fungal products and infection preventionstrategies. The authors also identified that the concentration ofanti-fungal drug is a key determinant of its capacity to control thedevelopment of the biofilms. For example, the results indicated thatliposomal amphotericin B can control the formation of biofilms in C.auris when its concentration in raised from 0.25 to 16 mg per liter.An experiment to compare the severity of infections caused by C.auris and C. albicans indicated the earlier has the capacity to formbiofilms with a high level of virulence. These findings indicate thatnon-aggregative C. auris phenotype can form biofilms with improvedvirulence capacity, which distinguishes the pathogen from othermembers of Candida species.

Thefirst method used in the study involved the isolation of Candidapathogens and their propagation in the laboratory settings. Thereagent used in this method is YPD broth. Differences in the processand the size of biofilms in Candida species were then studied. Thenext method was the determination of antifungal susceptibility of C.auris,which was accomplished using the Clinical Laboratory StandardsInstitute M27-A3 broth microdilution. Other reagents used in thismethod are the serial 2-fold dilutions. Killing assay is the majormethod that was used to evaluate the pathogenicity of Candidaspecies. This method was based on Galleria mellonella.

Themain source of controversy in the study conducted by Sherry etal.(2017) is the fact that C. auris was found to have less capacity toform biofilm of the same size as C.albicans,but it was more virulent than other Candida pathogens. Therefore, therole of biofilms in the determination of virulence as well as drugresistance in Candida species need to be clarified in the futurestudies.

DiscussionQuestions

Thetwo studies that were conducted by Chattterjee etal.(2015) and Sherry etal.(2017) complement each other by showing that C.aurisis a major cause of hospital-based infections. The findings of bothstudies indicate that the formation of biofilms is the keydeterminant of the capacity of Candida species (including C.auris)to express their virulence and resistance. In addition, authors ofthe two articles acknowledge the fact that it is difficult todiagnose or distinguish C.aurisinfection from the rest of Candida pathogens using traditionalmethods that are applied in the clinical settings. Therefore, thefindings reported in the two articles lead to an argument that genomesequence is the most reliable approach for conducting differentialdiagnosis of Cauris.

However,the study conducted by Sherry etal.(2017) contradicted the one that was done by Chattterjee etal.(2015) by showing that the formation of biofilms may not be the soledeterminant of virulence. Sherry etal.(2017) advanced this argument by showing that C.aurisproduces less biofilm, but it is more virulent than C.albicans.These findings contradict the study conducted by Chattterjee etal.(2015) by raising doubts as to whether targeting genetic expressionsthat lead to the development of biofilms can be a reliable approachfor conducting the differential diagnosis and preventinghospital-based infections that are associated with C.auris.

Thetwo studies make a significant contribution to the field of fungalpathogens by indicating the severity of hospital-based infectionsthat are associated with C.auris,suggesting effective prevention methods, and an approach that can beused to conduct a successful differential diagnosis. Researchers inthe two studies resolve the difficulty of differentiating theinfection caused by C.aurisand other Candida pathogens by showing how they differ in genomesequence. Therefore, they make a contribution by indicating that theanalysis of the genetic composition of individual pathogens can beused to distinguish between their infections. The successfuldiagnosis of the infection will go a long way in facilitatingeffective treatment and prevention of further spreading of thepathogen in the health care facilities.

Althoughtwo studies provide a significant insight into the virulence of C.auris and its diagnosis, they can be improved in the future byadopting a different methodology that will eliminate bias. Therefore,a new study should be conducted using an alternative research design,such as randomized control trials. It is evident that the authors ofthe two articles relied on the experimental design to conduct theirstudy. This design is associated with several limitations, such asthe creation of artificial situations that enable the researchers totake control of the variables and participants. The experimentaldesign is also associated with human errors since researchers areextensively involved in the process of collecting data. Therefore,the reliability of the findings can be improved by using a differentdesign that will reduce bias.

Thereis one major recommendation for the future studies that can lead toan increase in the reliability as well as the credibility of thefindings. The future studies should conduct the functionalclassification of all proteins that form the structure of C.auris.Chattterjee etal.(2015) held that most of the proteins are functionallyuncharacterized. Sherry etal.(2017), on the other hand, identified that the formation of biofilmsmay not be the only factor that determines the level of virulence ofdifferent Candida species. Therefore, the functions of theunclassified proteins should be determined in order to find outwhether they contribute towards the level of virulence of thepathogen.

Conclusion

Candidaauris is one of the most common types of pathogens that causenosocomial infections. It is more dangerous than other Candidaspecifies because of its high level of virulence. It infects patientsby producing biofilms. The two studies reviewed in this paper provideevidence-based findings on nosocomial infection that is caused by C.auris.This is a critical issue in the health care sector since itcomplicates the treatment process. The findings reported byChattterjee etal.(2015) provide a significant insight into how C.aurisinfection can be distinguished from illnesses caused by other Candidapathogens. The use of traditional methods complicates differentialdiagnosis while the analysis of genome sequence leads to accurateidentification of C.auris.The findings reported by Sherry etal.(2017) on the other hand, lead to an argument that the use ofanti-fungi to control hospital-based infections cannot be effective,unless prevention measures are taken.

References

Chattterjee,S., Alampalli, S., Nageshan, R., Chettiar, T., Joshi, S. &amp Tatu,S. (2015). Draft genome of a commonly misdiagnosed multidrug pathogenCandidaauris.BMCGenomics, 16,1-16. DOI 10.1186/s12864-015-1863-z

Sherry,L., Ramage, G., Kean, R., Borman, A., Johnson, M., Richardson, D. &ampRautemaa-Richardson, R. (2017). Bioform-forming capability of highlyvirulent, multidrug-resistant Candidaauris.EmergingInfectious Diseases,23 (2), 328-331.