
Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown
Published: May 7, 2024
Language: Английский
Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown
Published: May 7, 2024
Language: Английский
International Journal of Antimicrobial Agents, Journal Year: 2024, Volume and Issue: 64(3), P. 107275 - 107275
Published: July 14, 2024
Language: Английский
Citations
12Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15
Published: March 15, 2024
Klebsiella pneumoniae is among the most relevant pathogens worldwide, causing high morbidity and mortality, which worsened by increasing rates of antibiotic resistance. It a constituent host microbiota different mucosa, that can invade cause infections in many sites. The development new treatments prophylaxis against this pathogen rely on animal models to identify potential targets evaluate efficacy possible side effects therapeutic agents or vaccines. However, validity data generated highly dependable choosing adequately reproduce hallmarks human diseases. present review summarizes current knowledge used investigate K. infections, with focus mucosal advantages limitations each model are discussed compared; applications, extrapolations subjects future modifications improve techniques also presented. While mice widely species studies, they such as natural resistance difficulties reproducing main steps infections. Other models, Drosophila melanogaster (fruit fly), Caenorhabditis elegans, Galleria mellonella Danio rerio (zebrafish), contribute understanding specific aspects infection process, bacterial lethality colonization innate immune system response, however, but do not immunological complexity mammals. In conclusion, choice will depend mainly questions being addressed study, while better interplay between virulence factors responses provide deeper comprehension disease process aid effective preventive/therapeutic strategies.
Language: Английский
Citations
10PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(4), P. e1011900 - e1011900
Published: April 5, 2024
In vivo single-cell approaches have transformed our understanding of the immune populations in tissues. Mass cytometry (CyTOF), that combines resolution mass spectrometry with ability to conduct multiplexed measurements cell molecules at single resolution, has enabled resolve diversity subsets, and their heterogeneous functionality. Here we assess feasibility taking CyTOF one step further immuno profile cells while tracking interactions bacteria, a method term Bac-CyTOF. We focus on pathogen Klebsiella pneumoniae interrogating pneumonia mouse model. Using Bac-CyTOF, unveil atlas mice infected K . hypervirulent strain. The is characterized by decrease alveolar monocyte-derived macrophages. Conversely, neutrophils, inflammatory monocytes are an increase subpopulations expressing markers less active such as checkpoint PD-L1. These infected. show type VI secretion system (T6SS) contributes shape lung landscape. T6SS governs interaction monocytes/macrophages shifting from macrophages interstitial limiting infection monocytes. lack results cells, By probing , Acinetobacter baumannii strains limited survive vivo, uncover heightened recruitment relative high levels eosinophils characteristic subpopulation neutrophils features clearing infections. leverage Bac-CyTOF-generated knowledge platform investigate role DNA sensor STING sting -/- present consistent including reduced absence facilitates clearance.
Language: Английский
Citations
5Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: Jan. 22, 2025
Microbial species must compete for space and nutrients to persist in the gastrointestinal (GI) tract, our understanding of complex pathobiont-microbiota interactions is far from complete. Klebsiella pneumoniae, a problematic, often drug-resistant nosocomial pathogen, can colonize GI tract asymptomatically, serving as an infection reservoir. To provide insight on how K. pneumoniae interacts with resident gut microbiome, we conduct transposon mutagenesis screen using murine model colonization intact microbiota. Among genes identified were those encoding type VI secretion system (T6SS), which mediates contact-dependent killing gram-negative bacteria. From several approaches, demonstrate that T6SS critical colonization. Metagenomics vitro assays reveal reduces Betaproteobacteria T6SS-dependent manner, thus identifying specific targeted by pneumoniae. We further show gene expression controlled transcriptional regulators only occurs under conditions mimic environment. By enabling thrive gut, indirectly contributes pathogenic potential this organism. These observations advance molecular successfully colonizes tract. Through metagenomics, Bray et al. interacting microbiota partners revealed role its colonization, t6ss transcription occurring GI-mimetic conditions.
Language: Английский
Citations
0mBio, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 29, 2025
ABSTRACT The emergence and global spread of carbapenem-resistant Enterobacter cloacae complex species present a pressing public health challenge. Carbapenem-resistant spp. cause wide variety infections, including septic shock fatalities in newborns immunocompromised adults. intestine may be major reservoir for these resistant strains, either by facilitating contamination fomites transfer to susceptible individuals, or through translocation from the gut bloodstream. For this reason, we sought establish neonatal mouse model investigate mechanisms underpinning colonization hormaechei . We describe new study spp., leading vital insights into adaptation E. environment during early stages intestinal colonization. observed successful proliferation 5-day-old infant gut, with primary localization colon following oral inoculation. also uncovered evidence that uses mucus as carbon source colon. Our findings underscore importance oxygen-dependent metabolic pathways, pyruvate dehydrogenase N- acetyl-D-glucosamine metabolism, proliferation, which aligns previous human studies. These are essential developing novel therapeutic strategies can serve decolonization therapies at-risk populations. IMPORTANCE Bloodstream infections caused pose significant clinical threat. acts site serves infection. To combat pathogen, it is crucial understand how colonize such knowledge pave way alternative targets. In study, developed gastrointestinal discovered plays key role Additionally, identified two catabolism pathways contribute This offers valuable host-pathogen interactions helps identify critical fitness factors , potentially guiding development vaccines minimize carriage patient populations at risk infection
Language: Английский
Citations
0Trends in Microbiology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Klebsiella pneumoniae (KP) is a global threat to human health due the isolation of multidrug-resistant strains. Despite advancements in understanding KP's population structure, antibiotic resistance mechanisms, and transmission patterns, gap remains how KP evades defenses, allowing pathogen flourish tissues despite an activated immune system. infection biology has been shaped by notion that evolved shield from defenses more than actively suppress them. This review describes new paradigms exploits coevolution with innate system hijack effectors receptors ablate signaling pathways counteract cell-intrinsic immunity, making apparent can no longer be considered only as stealth pathogen.
Language: Английский
Citations
0The Microbe, Journal Year: 2025, Volume and Issue: unknown, P. 100274 - 100274
Published: Feb. 1, 2025
Language: Английский
Citations
0mLife, Journal Year: 2025, Volume and Issue: unknown
Published: March 18, 2025
The escalating antibiotic resistance crisis poses a major global health threat. Bacteriophage therapy offers promising alternative for combating multidrug-resistant infections. However, bacterial to phages remains significant hurdle. Innovative strategies are needed overcome this challenge. In study, we developed phage cocktail based on our library, consisting of three that suppressed carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp). This capitalized dual instances collateral sensitivity, thereby constraining the evolution resistance. first-layered sensitivity arose from overlapping coverage between capsular polysaccharide (CPS) and lipopolysaccharide (LPS), rendering bacteria resistant CPS-binding but more susceptible LPS-binding phages. second-layered resulted an O serotype switch (from O1 O2), causing antigen-binding increasing susceptibility target O2 antigen. dual-layered effectively mitigated infection caused by CR-hvKp in mice. Our research highlights importance mechanism counteracting sophisticated strategy configuring cocktails eliminate
Language: Английский
Citations
0Microbial Pathogenesis, Journal Year: 2025, Volume and Issue: unknown, P. 107510 - 107510
Published: March 1, 2025
Language: Английский
Citations
0Future Microbiology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13
Published: March 26, 2025
Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) combines high pathogenicity with multidrug resistance to become a new superbug. MDR-hvKP reports continue emerge, shattering the perception that K. (hvKP) strains are antibiotic sensitive. Patients infected have been reported in Asia, particularly China. Although hvKP can acquire drug genes, seems be more easily transformed from classical (cKP), which has strong gene uptake ability. To better understand biology of MDR-hvKP, this review discusses virulence factors, mechanisms, formation pathways, and identification MDR-hvKP. Given their destructive transmissible potential, continued surveillance these organisms enhanced control measures should prioritized.
Language: Английский
Citations
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