Measuring bacterial growth rates is routine, however, determining growth rates during infection in host has been more challenging. Peak-to-trough ratio (PTR) is a technique for studying microbial growth dynamics, calculated using the ratio of replication origin () copies to that of the terminus (), as originally defined by whole genome sequencing (WGS). WGS presents significant challenges in terms of expense and data analysis complexity due to the presence of host DNA in the samples.
View Article and Find Full Text PDFBloodstream infections (BSIs) are common in hospitals, often life-threatening and increasing in prevalence. Microorganisms in the blood are usually rapidly cleared by the immune system and filtering organs but, in some cases, they can cause an acute infection and trigger sepsis, a systemic response to infection that leads to circulatory collapse, multiorgan dysfunction and death. Most BSIs are caused by bacteria, although fungi also contribute to a substantial portion of cases.
View Article and Find Full Text PDFUnlabelled: More than half of women will experience a urinary tract infection (UTI) with most cases caused by uropathogenic (UPEC). Bacterial swimming motility enhances UPEC pathogenicity, resulting in more severe disease outcomes including kidney infection. Surprisingly, the connection between motility and iron limitation is mostly unexplored despite the lack of free iron available in the host.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2024
Urinary tract infections (UTI) account for a substantial financial burden globally. Over 75% of UTIs are caused by uropathogenic (UPEC), which have demonstrated an extraordinarily rapid growth rate in vivo. This rapid growth rate appears paradoxical given that urine and the human urinary tract are relatively nutrient-restricted.
View Article and Find Full Text PDFUnlabelled: A hallmark of infection of the urinary tract is the formation of stones. The ability to induce urinary stone formation requires urease, a nickel metalloenzyme that hydrolyzes urea. This reaction produces ammonia as a byproduct, which can serve as a nitrogen source and weak base that raises the local pH.
View Article and Find Full Text PDFAnimal models for host-microbial interactions have proven valuable, yielding physiologically relevant data that may be otherwise difficult to obtain. Unfortunately, such models are lacking or nonexistent for many microbes. Here, we introduce organ agar, a straightforward method to enable the screening of large mutant libraries while avoiding physiological bottlenecks.
View Article and Find Full Text PDFUnlabelled: More than half of all women will experience a urinary tract infection (UTI) in their lifetime with most cases caused by uropathogenic (UPEC). Bacterial motility enhances UPEC pathogenicity, resulting in more severe disease outcomes including kidney infection. Surprisingly, the connection between motility and iron limitation is mostly unexplored, despite the lack of free iron available in the host.
View Article and Find Full Text PDFis a hospital-associated pathogen primarily causing urinary tract infections (UTIs), pneumonia, and septicemia. Two challenging lineages include the hypervirulent strains, causing invasive community-acquired infections, and the carbapenem-resistant classical strains, most frequently isolated from UTIs. While hypervirulent strains are often characterized by a hypermucoid phenotype, classical strains usually present with low mucoidy.
View Article and Find Full Text PDFHealthcare-acquired infections are a leading cause of disease in patients that are hospitalized or in long-term-care facilities. Klebsiella pneumoniae (Kp) is a leading cause of bacteremia, pneumonia, and urinary tract infections in these settings. Previous studies have established that the operon, a genetic locus that confers tellurite oxide (KTeO) resistance, is associated with infection in colonized patients.
View Article and Find Full Text PDFFor women in the United States, urinary tract infections (UTIs) are the most frequent diagnosis in emergency departments, comprising 21.3% of total visits. Uropathogenic Escherichia coli (UPEC) causes ~80% of uncomplicated UTIs.
View Article and Find Full Text PDFOrdered transposon libraries are a valuable resource for many bacterial species, especially those with difficult methods for generating targeted genetic mutations. Here, we present the construction of an ordered transposon library for the bacterial urinary tract pathogen Proteus mirabilis strain HI4320. This library will facilitate future studies into P.
View Article and Find Full Text PDFKlebsiella pneumoniae is a leading cause of Gram-negative bacteremia, which is a major source of morbidity and mortality worldwide. Gram-negative bacteremia requires three major steps: primary site infection, dissemination to the blood, and bloodstream survival. Because K.
View Article and Find Full Text PDFThe human gut acts as the main reservoir of microbes and a relevant source of life-threatening infections, especially in immunocompromised patients. There, the opportunistic fungal pathogen adapts to the host environment and additionally interacts with residing bacteria. We investigated fungal-bacterial interactions by coinfecting enterocytes with the yeast and the Gram-negative bacterium resulting in enhanced host cell damage.
View Article and Find Full Text PDFMore than half of women will experience a urinary tract infection (UTI), with uropathogenic Escherichia coli (UPEC) causing ~80% of uncomplicated cases. Iron acquisition systems are essential for uropathogenesis, and UPEC strains encode highly diverse iron acquisition systems, underlining their importance. However, a recent UPEC clinical isolate, HM7, lacks this diversity and instead encodes the synthesis pathway for a sole siderophore, enterobactin.
View Article and Find Full Text PDFCpxRA is an envelope stress response system that is highly conserved in the . CpxA has kinase activity for CpxR and phosphatase activity for phospho-CpxR (CpxR-P), a transcription factor. In response to membrane stress, CpxR-P is produced and upregulates genes involved in membrane repair and downregulates genes that encode virulence factors that are trafficked across the cell membrane.
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