Explore the vast range of titles available.

Antimicrobial and antifungal species are essential members of the healthy human microbiota. Several different species of lactobacilli that naturally inhabit the human body have been explored for their probiotic capabilities including strains of the species . However, (identified by 16S rRNA gene sequencing) has been associated with urogenital symptoms. Recently a new sister taxon of was described: . is also posited to have probiotic qualities. Here, we present a genomic investigation of all (  = 79) publicly available genome assemblies for both species. These strains include isolates from the vaginal tract, gastrointestinal tract, urinary tract, oral cavity, wounds, and lungs. The two species cannot be distinguished from short-read sequencing of the 16S rRNA as the full-length gene sequences differ only by two nucleotides. Based upon average nucleotide identity (ANI), we identified 20 strains deposited as that are in fact representatives of . Investigation of the genic content of the strains of these two species suggests recent divergence and/or frequent gene exchange between the two species. The genomes frequently harbored intact prophage sequences, including prophages identified in strains of both species. To further explore the antimicrobial potential associated with both species, genome assemblies were examined for biosynthetic gene clusters. Gassericin T and S were identified in 46 of the genome assemblies, with all strains including one or both bacteriocins. This suggests that the properties once ascribed to may better represent the species.

Human immunodeficiency virus (HIV) relies upon a broad array of host factors in order to replicate and evade the host antiviral response. Cleavage and polyadenylation specificity factor 6 (CPSF6) is one such host factor that is recruited by incoming HIV-1 cores to regulate trafficking, nuclear import, uncoating, and integration site selection. Despite these well-described roles, the impact of CPSF6 perturbation on HIV-1 infectivity varies considerably by cell type. Here, we report that CPSF6 knock-out in primary CD4+ T cells leads to increased permissivity to HIV-1 infection due to broad transcriptional reprogramming. Knock-out of CPSF6 results in widespread differential gene expression, including downregulation of genes involved in the innate immune response and enhanced expression of the HIV-1 co-receptors. Accordingly, these cells are less responsive to interferon and express lower levels of antiretroviral restriction factors, including TRIM5α. These transcriptional changes are linked to global shortening of mRNA 3' untranslated regions (UTRs) through changes in alternative polyadenylation (APA), which are triggered by disruption of the CPSF6-containing Cleavage Factor Im (CFIm) complex. Furthermore, we find that recruitment of CPSF6 by HIV-1 cores is sufficient to perturb CPSF6 function, leading to 3' UTR shortening and subsequent transcriptional rewiring. These results suggest a model in which HIV-1 transcriptionally reprograms target cells through recruitment of CPSF6 to incoming cores to circumvent the antiviral response and enhance permissivity to infection.

The recognition of the Aerococcus urinae complex (AUC) as an emerging uropathogen has led to growing concerns due to a limited understanding of its disease spectrum and antibiotic resistance profiles. Here, we investigated the prevalence of macrolide resistance within urinary AUC isolates, shedding light on potential genetic mechanisms. Phenotypic testing revealed a high rate of macrolide resistance: 45%, among a total of 189 urinary AUC isolates. Genomic analysis identified integrative and conjugative elements (ICEs) as carriers of the macrolide resistance gene ermA, suggesting horizontal gene transfer as a mechanism of resistance. Furthermore, comparison with publicly available genomes of related pathogens revealed high ICE sequence homogeneity, highlighting the potential for cross-species dissemination of resistance determinants. Understanding mechanisms of resistance is crucial for developing effective surveillance strategies and improving antibiotic use. Furthermore, the findings underscore the importance of considering the broader ecological context of resistance dissemination, emphasizing the need for community-level surveillance to combat the spread of antibiotic resistance within the urinary microbiome.

Bacterial species inhabit both the “healthy” and symptomatic female urinary tract. Lactobacillus species are frequently dominant members of the healthy urinary tract microbiota (urobiome), and thus have been associated with the lack of lower urinary tract symptoms (LUTS). In contrast, colonization by Escherichia coli is the most common cause of urinary tract infections (UTIs). Prior research has found that strains of Lactobacillus can inhibit the growth of uropathogens such as E. coli as well as vaginosis-associated pathogens. Investigations into the means by which lactobacilli inhibit pathogenic growth have primarily focused on their production of hydrogen peroxide (H2O2) and lactic acid, although other metabolites have been identified. This project explored how the secreted compounds of urinary strains of Lactobacillus species affect the growth of urinary E. coli. 53 different E. coli strains, isolated from urine samples of females with and without LUTS, were grown with the cell-free supernatant (CFS) of 42 different urinary lactobacilli strains. These lactobacilli included strains of the species L. crispatus, L. gasseri, L. jensenii, L. johnsonii, L. mulieris, and L. paragasseri. Three scenarios were observed: (1) the CFS had no effect on the growth of the E. coli, (2) the CFS reduced the growth of the E. coli, and (3) the CFS inhibited growth or killed the E. coli. At least half of the Lactobacillus CFS + E. coli pairs tested resulted in inhibited or reduced E. coli growth. To determine how the CFS was inhibiting or reducing E. coli growth, we further explored the role that pH and protein-based constituents of the CFS played. Evidence of phage induction caused by Lactobacillus CFS was found identifying a means in which lactobacilli can reduce or inhibit E. coli growth. To expand on these results, we tested L. mulieris UMB7784 CFS on another uropathogen, Aerococcus urinae. These experiments demonstrated evidence of this strain of Lactobacillus CFS negatively impacting the growth of A. mictus. This study furthers our understanding of interactions between microbes within the urinary microbiome.

The recognition of the Aerococcus urinae complex (AUC) as an emerging uropathogen has led to growing concerns due to a limited understanding of its disease spectrum and antibiotic resistance profiles. Here, we investigated the prevalence of macrolide resistance within urinary AUC isolates, shedding light on potential genetic mechanisms. Phenotypic testing revealed a high rate of macrolide resistance: 45%, among a total of 189 urinary AUC isolates. Genomic analysis identified integrative and conjugative elements (ICEs) as carriers of the macrolide resistance gene ermA, suggesting horizontal gene transfer as a mechanism of resistance. Furthermore, comparison with publicly available genomes of related pathogens revealed high ICE sequence homogeneity, highlighting the potential for cross-species dissemination of resistance determinants. Understanding mechanisms of resistance is crucial for developing effective surveillance strategies and improving antibiotic use. Furthermore, the findings underscore the importance of considering the broader ecological context of resistance dissemination, emphasizing the need for community-level surveillance to combat the spread of antibiotic resistance within the urinary microbiome.