Rhoades, N. S. | Search bioRxiv

bioRxiv2021

Acute SARS-CoV-2 infection is associated with an expansion of bacteria pathogens in the nose including Pseudomonas aeruginosa

Much of the research conducted on SARS-CoV-2 and COVID-19 has focused on the systemic host response, especially that generated by severely ill patients. Very few studies have investigated the impact of acute SARS-CoV-2 within the nasopharynx, the site of initial infection and viral replication. In this study we profiled changes in the nasal microbial communities as well as in host transcriptional profile during acute SARS-CoV-2 infection using 16S amplicon sequencing and RNA sequencing. These analyses were coupled to viral genome sequencing. Our microbiome analysis revealed that the nasal microbiome of COVID patients was unique and was marked by an expansion of bacterial pathogens. Some of these microbes (i.e. Acinetobacter) were shared with COVID negative health care providers from the same medical center but absent in COVID negative outpatients seeking care at the same institutions suggesting acquisition of nosocomial respiratory pathogens. Specifically, we report a distinct increase in the prevalence and abundance of the pathogen Pseudomonas aeruginosa in COVID patients that correlated with viral RNA load. These data suggest that the inflammatory environment caused by SARS-CoV-2 infection and potentially exposure to the hospital environment leads to an expansion of bacterial pathogens in the nasal cavity that could contribute to increased incidence of secondary bacterial infections. Additionally, we observed a robust host transcriptional response in the nasal epithelia of COVID patients, indicative of an antiviral innate immune repones and neuronal damage. Finally, analysis of viral genomes did not reveal an association between viral loads and viral sequences.

microbiology↗

bioRxiv2020

Longitudinal profiling of the macaque vaginal microbiome reveals similarities to diverse human vaginal communities: implications for use as a pre-clinical model for bacterial vaginosis

The vaginal microbiota plays an important role in womens reproductive and urogenital health. Disturbances in this microbial community can lead to several adverse outcomes including pelvic inflammatory disease, bacterial vaginosis (BV) as well as increased susceptibility to sexually transmitted infections, miscarriage, and pre-term births. It is now well accepted that while the microbiome of healthy women in the developed world is dominated by Lactobacillus species, vaginal communities in asymptomatic women, especially those in the developing world, can be comprised of a diverse set of micro-organisms. The presence of a diverse vaginal microbiome has been associated with increased susceptibility to HIV infection but their implications for womens health remain poorly understood. Rhesus macaques are an excellent translational animal model due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from 16 reproductive age female rhesus macaques. Many animals showed hallmarks of BV, including Nugent scores above 7 and high vaginal pH. At both the taxonomic and functional level, the rhesus macaque vaginal microbiome was most similar to that of women who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Specifically, rhesus macaque vaginal microbiomes harbored a diverse set of anaerobic gram-negative bacteria, including; Snethia, Prevotella, Porphyromonas, and Mobilluncus. Interestingly, some animals were transiently colonized by Lactobacillus and some with Gardnerella. Our in-depth and comprehensive analysis highlights the importance of the model to test interventions for manipulating the vaginal microbiome. IMPORTANCEIt is widely accepted that the "healthy" vaginal microbiome of the majority of women in the developed world is dominated by Lactobacillus species. However, in the developing world, a majority of women are colonized by diverse microbial communities, typically associated with bacterial vaginosis, but remain asymptomatic. Many questions remain about the drivers of this disparity and potential interventions to alter the vaginal microbiome. Rhesus macaques provide an excellent translational model due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from a large cohort of reproductive age rhesus macaques. At the taxonomic, genomic, and functional level, the rhesus macaque vaginal microbiome was most similar to that of humans who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Our in-depth and comprehensive analysis highlights the utility of macaques to test interventions for manipulating the vaginal microbiome.

microbiology↗