Nontyphoidal (NTS) strains are associated with gastroenteritis worldwide but are also the leading cause of bacterial bloodstream infections in sub-Saharan Africa. The invasive NTS (iNTS) strains that cause bloodstream infections differ from standard gastroenteritis-causing strains by >700 single-nucleotide polymorphisms (SNPs). These SNPs are known to alter metabolic pathways and biofilm formation and to contribute to serum resistance and are thought to signify iNTS strains becoming human adapted, similar to typhoid fever-causing strains. Identifying SNPs that contribute to invasion or increased virulence has been more elusive. In this study, we identified a SNP in the cache 1 signaling domain of diguanylate cyclase STM1987 in the invasive serovar Typhimurium type strain D23580. This SNP was conserved in 118 other iNTS strains analyzed and was comparatively absent in global Typhimurium isolates associated with gastroenteritis. STM1987 catalyzes the formation of bis-(3',5')-cyclic dimeric GMP (c-di-GMP) and is proposed to stimulate production of cellulose independent of the master biofilm regulator CsgD. We show that the amino acid change in STM1987 leads to a 10-fold drop in cellulose production and increased fitness in a mouse model of acute infection. Reduced cellulose production due to the SNP led to enhanced survival in both murine and human macrophage cell lines. In contrast, loss of CsgD-dependent cellulose production did not lead to any measurable change in fitness. We hypothesize that the SNP in represents a pathoadaptive mutation for iNTS strains.
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http://dx.doi.org/10.1128/IAI.00810-20 | DOI Listing |
Microorganisms
June 2024
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Pathogenic strains causing gastroenteritis typically can colonize and proliferate in the intestines of multiple host species. They retain the ability to form red dry and rough () biofilms, as seen in serovar Typhimurium. Conversely, serovar like Typhi, which can cause systemic infections and exhibit host restriction, are -negative.
View Article and Find Full Text PDFInvasive nontyphoidal (iNTS) causes significant concern with ~15% morbidity, affecting populations mainly in African countries. However, iNTS infections among the Chinese pediatric population remain largely unknown. Here, we conducted a genomic investigation to study pediatric iNTS infections in a Chinese hospital.
View Article and Find Full Text PDFGut Microbes
May 2024
Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ, USA.
The ability of bacteria to sense and respond to mechanical forces has important implications for pathogens during infection, as they experience wide fluid shear fluctuations in the host. However, little is known about how mechanical forces encountered in the infected host drive microbial pathogenesis. Herein, we combined mathematical modeling with hydrodynamic bacterial culture to profile transcriptomic and pathogenesis-related phenotypes of multidrug resistant .
View Article and Find Full Text PDFFront Nutr
May 2024
Department of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Introduction: Monosodium glutamate (MSG), an umami substance, stimulates the gut-brain axis communication via gut umami receptors and the subsequent vagus nerves. However, the brain mechanism underlying the effect of MSG ingestion during the developmental period on aggression has not yet been clarified. We first tried to establish new experimental conditions to be more appropriate for detailed analysis of the brain, and then investigated the effects of MSG ingestion on aggressive behavior during the developmental stage of an ADHD rat model.
View Article and Find Full Text PDFZhonghua Liu Xing Bing Xue Za Zhi
April 2024
Guangdong Provincial Center for Disease Control and Prevention, Guangdong Provincial Key Laboratory of Pathogen Detection for Emerging Infectious Disease Response, Guangzhou 510080,China.
To understand the serotype distribution, drug resistance and molecular characterization of invasive non-typhoid (iNTS) in Guangdong Province from 2018 to 2022 and provide scientific evidence for the prevention and treatment of blood flow infection caused by . Serological identification, antimicrobial susceptibility testing, multilocus sequence typing (MLST), and whole genome sequencing were performed on isolated from blood and stool samples in Guangdong from 2018 to 2022. Simultaneously, annotated the sequencing results for drug resistance genes and virulence factors by a microbial gene annotation system.
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