Antibiotic-recalcitrant infections, defined as the prolonged carriage of pathogenic bacteria even in the presence of antibiotics, are often caused by bacteria that are genetically susceptible to the drug. These recalcitrant bacteria fail to proliferate in the presence of antibiotics but remain viable such that they may recolonize their niche following antibiotic withdrawal. Significant progress has been made in our understanding of antibiotic-recalcitrant Salmonella, which are thought to be the source of infection relapse.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2024
The rise of antimicrobial failure is a global emergency, and causes beyond typical genetic resistance must be determined. One probable factor is the existence of subpopulations of transiently growth-arrested bacteria, persisters, that endure antibiotic treatment despite genetic susceptibility to the drug. The presence of persisters in infected hosts has been successfully established, notably through the development of fluorescent reporters.
View Article and Find Full Text PDFTranscription factors control gene expression; among these, transcriptional repressors must liberate the promoter for derepression to occur. Toxin-antitoxin (TA) modules are bacterial elements that autoregulate their transcription by binding the promoter in a T:A ratio-dependent manner, known as conditional cooperativity. The molecular basis of how excess toxin triggers derepression has remained elusive, largely because monitoring the rearrangement of promoter-repressor complexes, which underpin derepression, is challenging.
View Article and Find Full Text PDFGenetically susceptible bacteria can escape the action of bactericidal antibiotics through antibiotic tolerance or persistence. However, one major difference between the two phenomena is their distinct penetrance within an isogenic population. While with antibiotic persistence, susceptible and persister cells co-exist, antibiotic tolerance affects the entire bacterial population.
View Article and Find Full Text PDFThe microbial cell surface is a site of critical microbe-host interactions that often control infection outcomes. Defining the set of host proteins present at this interface has been challenging. Here we used a surface-biotinylation approach coupled to quantitative mass spectrometry to identify and quantify both bacterial and host proteins present on the surface of diarrheal fluid-derived Vibrio cholerae in an infant rabbit model of cholera.
View Article and Find Full Text PDFToxin-antitoxin (TA) systems are a large family of genes implicated in the regulation of bacterial growth and its arrest in response to attacks. These systems encode nonsecreted toxins and antitoxins that specifically pair, even when present in several paralogous copies per genome. Salmonella enterica serovar Typhimurium contains three paralogous TacAT systems that block bacterial translation.
View Article and Find Full Text PDFThe function of , a bacterial gene predicted to encode an inner membrane protein, is largely unknown. Early studies in linked to Colicin V secretion and recent work revealed that it is required for robust intestinal colonization by diverse enteric pathogens. In enterohemorrhagic (EHEC), is required for resistance to the bile salt deoxycholate (DOC).
View Article and Find Full Text PDFDespite the advent of new techniques for genetic engineering of bacteria, allelic exchange through homologous recombination remains an important tool for genetic analysis. Currently, -based vector systems are often used for allelic exchange, but counterselection escape, which prevents isolation of cells with the desired mutation, occasionally limits their utility. To circumvent this, we engineered a series of "pTOX" allelic-exchange vectors.
View Article and Find Full Text PDFIntroduction: Preeclampsia represents a major public health burden worldwide, but predictive and diagnostic biomarkers are lacking. Metabolomics is emerging as a valuable approach to generating novel biomarkers whilst increasing the mechanistic understanding of this complex condition.
Objectives: To summarize the published literature on the use of metabolomics as a tool to study preeclampsia.