Transcriptomic Insights into Casein-Driven Adaptive Evolution of Burkholderia thailandensis: Implications for Biofilm Formation and Antibiotic Susceptibility.
It is demonstrated that casein-driven evolution selects for social 'cheaters' that conserve energy by downregulating costly virulence determinants, revealing a fundamental virulence-fitness trade-off.
Abstract
How nutrient stress shapes bacterial evolution and the associated fitness trade-offs remains a central question in microbiology. Using Burkholderia thailandensis as a surrogate for the pathogen B. pseudomallei, we performed adaptive laboratory evolution with casein as the sole carbon source. Over 30 days of serial passaging, the population shifted towards protease deficiency, with mutants constituting 54.94% by the endpoint. These evolved strains exhibited pleiotropic virulence attenuation-including reduced rhamnolipid production, motility, auto-aggregation, and biofilm formation-alongside increased susceptibility to imipenem and chloramphenicol. RNA-seq analysis of evolved strain E3101 revealed 2,836 differentially expressed genes, with significant downregulation of quorum sensing (AHL synthesis), rhamnosyltransferases, flagellar assembly, and biofilm regulatory pathways. Our findings demonstrate that casein-driven evolution selects for social 'cheaters' that conserve energy by downregulating costly virulence determinants, revealing a fundamental virulence-fitness trade-off. The coordinated transcriptional repression of biofilm and antibiotic resistance pathways provides a mechanistic framework for understanding bacterial adaptation strategies and potential therapeutic vulnerabilities in Burkholderia.
Phytopathogens encounter highly heterogeneous environments during infection. Carbon availability is a fundamental metabolic constraint that impacts bacterial virulence; however, the mechanism underlying the coordination of virulence traits based on metabolic cues remains unclear. We investigated the regulatory network of the soft-rot pathogen Pectobacterium carotovorum during Napa cabbage colonization, which generates tissue maceration with steep glucose and pectin gradients. Using GFP transcriptional fusions, we mapped the spatiotemporal expression of key regulatory (flhD, rsmA, and rsmB) and functional (fliC and pelA) virulence genes across necrotic lesions. As disease progressed, glucose and pectin accumulated at lesion centers before dissipating, establishing a distinct chemical zonation that mirrored virulence-gene profiles. Flagellar genes and rsmA showed consistent upregulation at lesion margins via the glucose-responsive cAMP-CRP system. In contrast, rsmB was upregulated at both centers and margins, whereas plant cell wall-degrading enzymes (PCWDEs) maintained relatively uniform expression. This spatial differentiation was driven by the concerted action of cAMP-CRP and pectin-responsive KdgR. cAMP-CRP disruption but not that of KdgR abolished the spatial organization of virulence gene expression and impaired lesion expansion, underscoring its central role in infection dynamics. Additionally, identification of previously unrecognized CRP-dependent targets reveals its expanded regulatory scope in Pectobacterium. These findings indicate a sophisticated spatiotemporal program where the interplay between cAMP-CRP and KdgR prioritizes motility at nutrient-depleted regions for outward expansion while sustaining PCWDE production across the lesion to maximize tissue maceration. This study highlights how carbon-responsive networks enable pathogens to exploit the complex chemical landscape of host tissues.
Yejin Park, Jae Hoon Lee· Microbiology Research· 0 citations
This review highlights SpoVG’s function in Staphylococcus, including its regulation of the expression of the adhesion factor gene sasC and the thermonuclease, which enables SpoVG to act as a molecular rheostat that influences biofilm formation and reduces acute virulence in response to environmental signals.
Abirami Karthikeyan, A. Javaid, G. N. A. Charway et al.· World Journal of Microbiolog...· 0 citations
Previous studies have demonstrated that quorum sensing (QS) can mitigate the impact of antibiotics on environmental microbial communities. Metagenomic analysis was used to examine AHL effects on the resistome in anaerobic fermentation microbiomes under antibiotic stress in this research. AHLs reduced ARGs, MGEs, and phage abundance compared to antibiotic-only samples following the addition of high concentrations (500 nmol/L) of AHLs. Phages and integrons played pivotal roles in shaping the resistome. Escherichia coli, Vibrio cholerae, and Pseudomonas aeruginosa were key targets affected by AHLs. Both the assembled environmental metagenomes and the complete genomes of isolated bacteria consistently support the broad potential of quorum-sensing systems in mediating the dissemination or regulation of resistome spreading. Quorum sensing systems are very likely to affect microbial community resistomes by regulating the phageome. These insights are valuable for refining fermentation and waste management processes, offering potential in environmental restoration and possibly curbing the spread of resistance genes.
Qin Zhou, Xiangyue Xu, Kun Mi et al.· Journal of Environmental Man...· 0 citations
While strain XJ-10 showed no detectable acylase activity, it exhibited significant degradation activity against AHL, suggesting a distinct QQ mechanism, and these findings broaden the scope of QQ-based biocontrol strategies and enhance mechanistic insights into managing bacterial diseases through QS modulation.
The genomes of pathogenic bacteria typically encode a diverse array of virulence factors, which constitute the fundamental basis for resisting host immunity and establishing infection. Given the high energetic cost of virulence gene expression, pathogens must precisely orchestrate the activation and silencing of these genes in accordance with the infection process, thereby flexibly executing diverse biological functions within the constraints of their energy budget. To sustain efficient infection, pathogens have evolved multiple mechanisms governing gene expression, enabling them to maintain competitive advantages over both their hosts and microbial competitors across diverse niches.
Pseudomonas plecoglossicida
is an important Gram-negative pathogen in aquaculture that combines strong environmental adaptability with host invasiveness. It frequently causes explosive epidemics such as visceral white spot disease, inflicting substantial economic losses, and represents one of the principal pathogens threatening the sustainability of aquaculture. An in-depth dissection of its complex virulence mechanisms and hierarchical regulatory networks will provide critical molecular insights into the dynamic interplay between
P. plecoglossicida
and its hosts. Accordingly, this review focuses on the key virulence factors of
P. plecoglossicida
, including secretion systems (the type III secretion system and its effector PP_ExoU, and the fish-pathogen-specific type VI secretion system T6SS-1), extracellular products, the flagellar system, metal nutrient acquisition systems, and outer membrane barriers, together with their hierarchical regulatory networks comprising sigma factors, two-component systems, quorum sensing, the second messenger cyclic di-GMP, and small RNAs. We summarize the core functions of these virulence factors and dissect the molecular mechanisms by which this pathogen senses environmental signals and modulates virulence expression, aiming to provide a theoretical basis for the development of novel antivirulence strategies and therapeutic interventions.
Unknown authors· Frontiers in Cellular and In...· 0 citations
ABSTRACT Successful gastrointestinal (GI) colonization by bacterial pathogens requires adaptation to nutrient competition and host-derived stresses in the gut, with adaptation via the bacterial stringent stress response playing a critical role. Epidemiological data suggest that the GI tract serves as a reservoir from which K. pneumoniae can spread and cause invasive disease or transmit to another host. DksA is a conserved stringent response transcriptional regulator that was identified in an in vivo transposon mutagenesis screen as an important K. pneumoniae gut determinant. However, its role in K. pneumoniae pathogenesis and gut colonization remain uncharacterized. Here, we demonstrate that DksA is required for survival against membrane-targeting antibiotics, consistent with a role in cell envelope stress tolerance. In addition, DksA positively influences capsule biosynthesis gene expression and hypermucoviscosity, and is essential for robust biofilm formation. Using a murine model, we establish that DksA functions as a determinant of GI colonization, despite disruption of the resident gut microbiota. Furthermore, we demonstrate that DksA is important for environmental survival and transmission by regulating RpoS, thereby providing a mechanistic link between the stringent stress response, environmental survival, and subsequent transmission. Together, these findings establish DksA as a central integrator of the stringent response, coordinating membrane stress resistance, virulence traits, and gastrointestinal colonization in K. pneumoniae.
Unknown authors· Infection and Immunity· 0 citations
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