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1. Oral Candida Predicts Streptococcus mutans Emergence in Underserved US Infants

   https://doi.org/10.1177/00220345211012385  

   Alkhars, N. ; Zeng, Y. ; Alomeir, N. ; Al Jallad, N. ; Wu, T.T. ; Aboelmagd, S. ; Youssef, M. ; Jang, H. ; Fogarty, C. ; Xiao, J. ( January 2021 , Journal of Dental Research)

   null (Ed.)

   Despite the cariogenic role of Candida suggested from recent studies, oral Candida acquisition in children at high risk for early childhood caries (ECC) and its association with cariogenic bacteria Streptococcus mutans remain unclear. Although ECC disproportionately afflicts socioeconomically disadvantaged and racial-minority children, microbiological studies focusing on the underserved group are scarce. Our prospective cohort study examined the oral colonization of Candida and S. mutans among 101 infants exclusively from a low-income and racial-minority background in the first year of life. The Cox hazard proportional model was fitted to assess factors associated with the time to event of the emergence of oral Candida and S. mutans. Oral Candida colonization started as early as 1 wk among 13% of infants, increased to 40% by 2 mo, escalated to 48% by 6 mo, and remained the same level until 12 mo. S. mutans in saliva was detected among 20% infants by 12 mo. The emergence of S. mutans by year 1 was 3.5 times higher (hazard ratio [HR], 3.5; confidence interval [CI], 1.1–11.3) in infants who had early colonization of oral Candida compared to those who were free of oral Candida ( P = 0.04) and 3 times higher (HR, 3.0; CI, 1.3–6.9) among infants whose mother had more than 3 decayed teeth ( P = 0.01), even after adjusting demographics, feeding, mother’s education, and employment status. Infants’ salivary S. mutans abundance was positively correlated with infants’ Candida albicans ( P < 0.01) and Candida krusei levels ( P < 0.05). Infants’ oral colonization of C. albicans was positively associated with mother’s oral C. albicans carriage and education ( P < 0.01) but negatively associated with mother’s employment status ( P = 0.01). Future studies are warranted to examine whether oral Candida modulates the oral bacterial community as a whole to become cariogenic during the onset and progression of ECC, which could lead to developing novel ECC predictive and preventive strategies from a fungal perspective. 

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2. Evolution and strain diversity advance exploration of Candida albicans biology

   https://doi.org/10.1128/msphere.00641-23  

   Anderson, Matthew Z ; Dietz, Siobhan M ( August 2024 , mSphere)

   Mitchell, Aaron P (Ed.)

   Fungi were some of the earliest organismal systems used to explore mutational processes and its phenotypic consequences on members of a species. Yeasts that cause significant human disease were quickly incorporated into these investigations to define the genetic and phenotypic drivers of virulence. AmongCandidaspecies,Candida albicanshas emerged as a model for studying genomic processes of evolution because of its clinical relevance, relatively small genome, and ability to tolerate complex chromosomal changes. Here, we describe major recent findings that used evolution of strains from defined genetic backgrounds to delineate mutational and adaptative processes and include how nascent exploration into naturally occurring variation is contributing to these conceptual frameworks. Ultimately, efforts to discern adaptive mechanisms used byC. albicanswill continue to divulge new biology and can better inform treatment regimens for the increasing prevalence of fungal disease.

    

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3. Gut microbiome composition of wild western lowland gorillas is associated with individual age and sex factors

   https://doi.org/10.1002/ajpa.23842  

   Pafčo, Barbora ; Sharma, Ashok_K ; Petrželková, Klára_J ; Vlčková, Klára ; Todd, Angelique ; Yeoman, Carl_J ; Wilson, Brenda_A ; Stumpf, Rebecca ; White, Bryan_A ; Nelson, Karen_E ; et al ( April 2019 , American Journal of Physical Anthropology)

   Environmental and ecological factors, such as geographic range, anthropogenic pressure, group identity, and feeding behavior are known to influence the gastrointestinal microbiomes of great apes. However, the influence of individual host traits such as age and sex, given specific dietary and social constraints, has been less studied. The objective of this investigation was to determine the associations between an individual's age and sex on the diversity and composition of the gut microbiome in wild western lowland gorillas.

   Publicly available 16S rRNA data generated from fecal samples of different groups ofGorilla gorillagorillain the Central African Republic were downloaded and bioinformatically processed. The groups analyzed included habituated, partially habituated and unhabituated gorillas, sampled during low fruit (dry,n = 28) and high fruit (wet,n = 82) seasons. Microbial community analyses (alpha and beta diversity and analyses of discriminant taxa), in tandem with network‐wide approaches, were used to (a) mine for specific age and sex based differences in gut bacterial community composition and to (b) asses for gut community modularity and bacterial taxa with potential functional roles, in the context of seasonal food variation, and social group affiliation.

   Both age and sex significantly influenced gut microbiome diversity and composition in wild western lowland gorillas. However, the largest differences were observed between infants and adults in habituated groups and between adults and immature gorillas within all groups, and across dry and wet seasons. Specifically, although adults always showed greater bacterial richness than infants and immature gorillas, network‐wide analyses showed higher microbial community complexity and modularity in the infant gorilla gut. Sex‐based microbiome differences were not evident among adults, being only detected among immature gorillas.

   The results presented point to a dynamic gut microbiome inGorillaspp., associated with ontogeny and individual development. Of note, the gut microbiomes of breastfeeding infants seemed to reflect early exposure to complex, herbaceous vegetation. Whether increased compositional complexity of the infant gorilla gut microbiome is an adaptive response to an energy‐limited diet and an underdeveloped gut needs to be further tested. Overall, age and sex based gut microbiome differences, as shown here, maybe mainly attributed to access to specific feeding sources, and social interactions between individuals within groups.

    

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4. The intersections of industrialization: Variation in skeletal indicators of frailty by age, sex, and socioeconomic status in 18th‐ and 19th‐century England

   https://doi.org/10.1002/ajpa.23881  

   Yaussy, Samantha L. ( June 2019 , American Journal of Physical Anthropology)

   Intersectionality theory argues that various categories of identity and forms of systemic oppression interact and produce inequalities in resource access, economic opportunities, and health outcomes. However, there has been little explicit engagement with this theory by bioarchaeologists examining disparate health outcomes in the past. This study examines the associations among frailty, age at death, sex, and socioeconomic status (SES) in 18th‐ and 19th‐century England.

   The sample for this study comes from four industrial‐era cemeteries from England, ca. 1711–1857. The associations among adult age (18+ years), SES, sex, and three skeletal indicators of stress (dental enamel hypoplasia [DEH,n= 293], cribra orbitalia [CO,n= 457], periosteal lesions [PNB,n= 436]) are examined using hierarchical log‐linear analysis.

   Significant interactions existed among the variables examined for two skeletal indicators: high SES females had lower frequencies of CO relative to other groups and males between ages 30–45 years exhibited higher frequencies of PNB compared to females or males of older or younger ages, regardless of SES. Additionally, sex and SES were consistently associated with age at death.

   These results suggest that patterns of stress indicators cannot be examined solely across unilateral axes of age, SES, or sex. Intersecting axes of privilege, marginalization, and structural oppression may have buffered high SES females from some negative health outcomes (CO) while predisposing them to others (risk of maternal mortality). Likewise, the hazardous working conditions relegated to adult males may have heightened the risk of injury, infection, and death for middle‐aged men in industrial‐era England.

    

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5. An expanded toolkit of drug resistance cassettes for Candida glabrata , Candida auris , and Candida albicans leads to new insights into the ergosterol pathway

   https://doi.org/10.1128/msphere.00311-23  

   Gregor, Justin B. ; Gutierrez-Schultz, Victor A. ; Hoda, Smriti ; Baker, Kortany M. ; Saha, Debasmita ; Burghaze, Madeline G. ; Vazquez, Cynthia ; Burgei, Kendra E. ; Briggs, Scott D. ( December 2023 , mSphere)

   Mitchell, Aaron P. (Ed.)

   The World Health Organization recently published the first list of priority fungal pathogens highlighting multipleCandidaspecies, includingCandida glabrata,Candida albicans, andCandida auris. However, prior studies in these pathogens have been mainly limited to the use of two drug resistance cassettes,NatMXandHphMX, limiting genetic manipulation capabilities in prototrophic laboratory strains and clinical isolates. In this study, we expanded the toolkit forC. glabrata,C. auris, andC. albicansto includeKanMXandBleMXwhen coupled with anin vitroassembled CRISPR-Cas9 ribonucleoprotein (RNP)-based system. Repurposing these drug resistance cassettes forCandida, we were able to make single gene deletions, sequential and simultaneous double gene deletions, epitope tags, and rescue constructs. We applied these drug resistance cassettes to interrogate the ergosterol pathway, a critical pathway for both the azole and polyene antifungal drug classes. Using our approach, we determined for the first time that the deletion ofERG3inC. glabrata,C. auris,andC. albicansprototrophic strains results in azole drug resistance, which further supports the conservation of the Erg3-dependent toxic sterol model. Furthermore, we show that anERG5deletion inC. glabratais azole susceptible at subinhibitory concentrations, suggesting that Erg5 could act as an azole buffer for Erg11. Finally, we identified a synthetic growth defect when bothERG3andERG5are deleted inC. glabrata,which suggests the possibility of another toxic sterol impacting growth. Overall, we have expanded the genetic tools available to interrogate complex pathways in prototrophic strains and clinical isolates.

   The increasing problem of drug resistance and emerging pathogens is an urgent global health problem that necessitates the development and expansion of tools for studying fungal drug resistance and pathogenesis. Prior studies inCandida glabrata,Candida auris, andCandida albicanshave been mainly limited to the use ofNatMX/SAT1andHphMX/CaHygfor genetic manipulation in prototrophic strains and clinical isolates. In this study, we demonstrated thatNatMX/SAT1, HphMX, KanMX,and/orBleMXdrug resistance cassettes when coupled with a CRISPR-ribonucleoprotein (RNP)-based system can be efficiently utilized for deleting or modifying genes in the ergosterol pathway ofC. glabrata,C. auris, andC. albicans. Moreover, the utility of these tools has provided new insights intoERGgenes and their relationship to azole resistance inCandida. Overall, we have expanded the toolkit forCandidapathogens to increase the versatility of genetically modifying complex pathways involved in drug resistance and pathogenesis.

    

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