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Study On The Molecular And Genetic Characteristics Of Oral Candida Spp. From Hainan Island

Posted on:2016-02-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:H M WangFull Text:PDF
GTID:1224330467993940Subject:Immunology
Abstract/Summary:PDF Full Text Request
Because most yeast infections are caused by endogenous strains, it is importantto understand the commensal yeast flora of hosts at the populationlevel.Understanding the commensal oral yeast flora could significantly increase ourability to design targeted prevention and treatment strategies. However,despite theirclinical significance, relatively little is known about the factors influencing yeastspecies distributions in humans. The objective of this study is to investigate thepotential contributions of host age, health status, and geography to yeast speciesdistribution in oral cavities of humans on the tropical Hainan Island located in theSouth China sea. Relatively little is known about the drug susceptibility profiles oforal yeasts in asymptomatic hospitalized patients.Since Hainan Island is located inChina’s southernmost province and separated from mainland China,it is a good placefor genetic study of yeast. The yeasts were investigated from the following4aspectsby using molecular biological methods.A.Oral yeast flora and its ITS sequence diversity among a health population inHainan Island,China:Here we report the oral yeast flora from the surveys of over1,000medicalstudents in Hainan Island,China. Our results showed that this population had a yeastcarriage rate (4.5%) much lower than other population samples reported previouslyfrom Mainland China (40–70%). In addition, C. albicans was isolated at a muchhigher frequency than those from other Chinese samples, with a frequency (80.9%)more similar to those in developed regions such a North America. The oral yeastcarriage rates and yeast species compositions were similar between male and femalestudents and between the hosts borne and raised on Hainan Island and those borne and raised on Mainland China. Furthermore, the sequence variation at the internaltranscribed spacer (ITS) regions of the nuclear ribosomal RNA gene cluster wasanalyzed for strains of the dominant species, C. albicans.Our analysis identified14ITS types among the41Hainan isolates of C. albicans.However, only four of the14ITS types were identical to those in reference strains from Europe and North America.Taken together, our analyses suggest that the oral yeast flora among host populationsin China is highly heterogeneous and that there is a high ITS sequence diversity in theHainan population of C. albicans.B.Patterns of Human Oral Yeast Species Distribution on Hainan Island inChina:Infections by yeast strains of the genus Candida are among the most prevalentfungal infections of humans. These yeasts are common residents of the oral mucosaand other body surfaces. Since most yeast infections are due to endogenous strainsand that species of Candida differ in virulence properties and in intrinsicsusceptibilities to antifungal drugs, understanding the human commensal yeast floracan help designing effective treatment and prevention strategies against yeastinfections. Here, we report the patterns of yeast species distributions in the oralcavities of1,799people from Hainan Island in southern China. Based on sequenceinformation at the fungal barcode locus ITS regions,368of the415obtained oralyeast strains were identified as belonging to26yeast species, while the remaining47strains all showed significant sequence divergence to the currently described species.The four most common yeast species were C. albicans (42%), C. tropicalis (20%), C.glabrata (5.5%), and C. Parapsilosis (4.1%) and10of the26yeast species wererepresented by only one strain each. Our analyses identified that the gender of hostsand ethnical background showed no contribution to oral yeast species distributions.However, the health status, place of birth, current residency, and the age of hosts allshowed significant contributions to the distributions of the four dominant yeastspecies.We compared our results with those reported previously and discussed thepotential mechanisms for the observed differences in oral yeast species distributions. C. Extensive genetic variation in the human pathogenic yeast Candida tropicalisfrom Hainan, China:This study analyzed the genetic diversity and relationships among isolates of theyeast pathogen Candida tropicalis from the southern Chinese island of Hainan. A totalof118isolates were obtained from seven geographic regions located across the majorregions in Hainan. DNA sequences at six loci (ICL1, MDR1, SAP2, SAP4, XYR1,and ZWF1) were obtained from each of the isolates. The sequence information wascompared with each other and with those in the C. tropicalis MLST database. A rangeof novel allelic sequences was found at each of the six loci (from6to52, with a meanof22.8new alleles per locus) absent in the existing MLST database representingstrains from other parts of the world. Our comparisons based on concatenatedsequences of the six loci identified that the118isolates belonged to117diploidsequence types. Importantly, none of the117diploid sequence types has beenreported from other geographic regions. Most of the genetic variation was foundwithin individual strains and there is abundant evidence for gene flow among theseven geographic locations. Our results indicate that the Hainan population of C.tropicalis contains abundant novel genetic variation.D.Drug resistance among oral yeasts from asymptomatic patients in HainanIsland,China:The oral cavity is a significant niche of the human microbiome and a gateway forthe microbiota in many other human body sites. As a result, understanding the oralmicrobiota has broad implications for the prevention and management of humaninfectious diseases. Opportunistic yeast infections are among the most prevalentfungal infections of humans and most opportunistic yeast pathogens are commonresidents of the oral mucosa. However, relatively little is known about the drugsusceptibility profiles of oral yeasts. Here, we report the species distribution andpatterns of antifungal susceptibility profiles among313yeasts isolated from the oralcavities of301asymptomatic hospitalized patients in Hainan province in southern China. These yeasts were tested for their susceptibilities to the following five drugs:amphotericin B, fluconazole, itraconazole, ketoconazole, and fluorocytosine.Sincenone of the sampled hosts had taken any antifungal drugs at least three months beforesamples were taken, we hypothesized that little or no drug resistance should beobserved. Contrary to our expectations, our analyses identified that29%(91/313) ofthe isolates were resistant to at least one drug and14.3%(45/313) were resistant totwo or more of the five common drugs. A high percentage of the isolated species(10/12,83.3%) had at least one isolate with the R and/or I phenotypes to at least oneof the five drugs. The potential sources of the observed resistance were discussed.From the studies above, we come to the following conclusions:1.As dominant specie for Candida spp, the Hainan population of C. albicans ishighly diverse and heterogeneous, which is not related with its geography and genderof the host.2.The health status, place of birth, current residency, and the age of hosts allshowed significant contributions to the diversity and the distributions of the Candidaspp.from Hainan Island.3.The Hainan population of C. tropicalis contains abundant novel geneticvariation.4.A high percentage(83.3%) of the isolated species from the asymptomatichospitalized patients in Hainan island had at least one isolate with the R and/or Iphenotypes to at least one of the five antifungal drugs. In addition to the highfrequencies of resistance to individual drugs, multidrug resistance was also commonamong the Hainan strains.Taken together, this study has demonstrated the patterns of human oral Candidaspecies distribution on Hainan Island in China, indicating the molecular geneticcharacteristics of diversity. The result provided the important clues and ideas forimproving our ability to design targeted prevention and treatment strategies...
Keywords/Search Tags:Candida, diversity, internal transcribed spacer (ITS), MLST, Hainan Island
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