PubMed · 7844800
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
1994. The enemy within.. https://pubmed.ncbi.nlm.nih.gov/7844800/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
UNLABELLED: Experimental infection models are widely used to investigate host-microbe interactions, often under the assumption that bacterial populations are genetically uniform. Here, we examined population heterogeneity in the widely used Helicobacter pylori strain PMSS1 and its relationship to variation in mouse infectivity. Single-colony isolates derived from PMSS1 displayed substantial differences in colonization efficiency, indicating that pre-existing variation within the population contributes to infection outcomes. To distinguish the effects of initial population heterogeneity from changes arising during infection, we analyzed PMSS2, a genetically homogeneous reference strain derived from PMSS1 that exhibited consistent infection phenotypes across independently isolated clones. Comparative genomic analysis of isolates recovered from infected mice revealed differences in the extent and patterns of genomic variation between PMSS1- and PMSS2-derived populations. These results demonstrate that variability in infection outcomes can arise from pre-existing heterogeneity within bacterial populations and highlight the importance of considering population composition when interpreting experimental infection studies. IMPORTANCE: Animal infection models are widely used to study how bacterial pathogens cause disease and change during infection. These studies often assume that the bacteria used for infection are genetically uniform. Our study shows that this assumption may not always hold. We found that a commonly used Helicobacter pylori strain contains hidden genetic diversity that leads to large differences in how well bacteria infect mice. By comparing this strain with a genetically uniform derivative, we show how differences present before infection can shape infection outcomes and influence the genetic changes observed during infection. Our findings highlight the importance of considering starting population diversity when interpreting experimental infection studies and are broadly relevant to research on microbial pathogenesis.
Exchange of genetic information by natural transformation shapes bacterial evolution. In Helicobacter pylori it is thought to drive its unusually high recombination rate, which has a crucial role in the evolution of virulence and the propagation of antibiotics resistance genes. While in most cases uptake of the incoming DNA into the periplasm is mediated by type IV pili, in H. pylori this initial step of natural transformation requires ComB, a unique competence-specific type IV secretion system (T4SS). The mechanisms by which ComB mediates DNA uptake are still poorly understood, since T4SS are usually involved in an opposite process of DNA export. Here, we identify a gene (hp1421) that is absolutely required for uptake of the transforming DNA into the periplasm, although distant from the comB operons. We show that hp1421 codes for a hexameric ATPase from the VirB11 family. HP1421 is present in the cytoplasm and interacts with ComB4, another ATPase of the T4SS inner membrane subcomplex. The structural modelling and functional analysis of HP1421 and its interaction with ComB4 indicate that HP1421 is a missing component of the ComB inner-membrane subcomplex that we propose to name ComB11. Phylogenetic analyses show that comB11 is a H. pylori core gene and suggest that the competence-dedicated ComB T4SS was a recent acquisition within Helicobacteraceae. Hence, co-option of the T4SS for DNA transformation requires nearly all the proteins that were previously essential for DNA conjugation.
Helicobacter pylori infection remains a major global health concern due to its association with gastric inflammation, ulceration, and gastric malignancies. This study evaluated the effects of Ngoc Linh ginseng (Panax vietnamensis Ha et Grushv.) root fractions on H. pylori virulence and host inflammatory responses. UHPLC-MS/MS-based metabolomic profiling coupled with feature-based molecular networking was employed to characterize the chemical profiles of different solvent fractions, identifying the dichloromethane (DCM) fraction as enriched in ginsenosides, particularly the ocotillol-type saponin majonoside R2 (MR2). In vitro assays showed that, despite minimal direct antibacterial activity, the DCM fraction at sub-inhibitory concentrations significantly reduced urease activity, acid tolerance, biofilm formation, and the expression of major virulence genes, including vacA and cagA. In H. pylori-infected AGS gastric epithelial cells, the DCM fraction and MR2 decreased VacA and CagA translocation, suppressed pro-inflammatory signaling and cytokine production, restored antioxidant defenses, and alleviated mitochondrial apoptosis. By contrast, ginsenoside Rg1 selectively modulated host inflammatory and oxidative stress responses without affecting bacterial virulence gene expression. These results demonstrate that Ngoc Linh ginseng root fractions mitigate H. pylori-induced pathogenic effects primarily through anti-virulence and host-directed mechanisms, highlighting their potential relevance for the development of gastric health-promoting functional products.