Bacterial Virulence Research Articles

Fluoromethylketone-Fragment Conjugates Designed as Covalent Modifiers of EcDsbA are Atypical Substrates.

Disulfide bond protein A (DsbA) is an oxidoreductase enzyme that catalyzes the formation of disulfide bonds in Gram-negative bacteria. In Escherichia coli, DsbA (EcDsbA) is essential for bacterial virulence, thus inhibitors have the potential to act as antivirulence agents. A fragment-based screen was conducted against EcDsbA and herein we describe the development of a series of compounds based on a phenylthiophene hit identified from the screen. A novel thiol reactive and "clickable" ethynylfluoromethylketone was designed for reaction with azide-functionalized fragments to enable rapid and versatile attachment to a range of fragments. The resulting fluoromethylketone conjugates showed selectivity for reaction with the active site thiol of EcDsbA, however unexpectedly, turnover of the covalent adduct was observed. A mechanism for this turnover was investigated and proposed which may have wider ramifications for covalent reactions with dithiol-disulfide oxidoreducatases.

Mycobacterium tuberculosis PhoP integrates stress response to intracellular survival by regulating cAMP level.

Survival of Mycobacterium tuberculosis within the host macrophages requires the bacterial virulence regulator PhoP, but the underlying reason remains unknown. 3',5'-Cyclic adenosine monophosphate (cAMP) is one of the most widely used second messengers, which impacts a wide range of cellular responses in microbial pathogens including M. tuberculosis. Herein, we hypothesized that intra-bacterial cAMP level could be controlled by PhoP since this major regulator plays a key role in bacterial responses against numerous stress conditions. A transcriptomic analysis reveals that PhoP functions as a repressor of cAMP-specific phosphodiesterase (PDE) Rv0805, which hydrolyzes cAMP. In keeping with these results, we find specific recruitment of the regulator within the promoter region of rv0805 PDE, and absence of phoP or ectopic expression of rv0805 independently accounts for elevated PDE synthesis, leading to the depletion of intra-bacterial cAMP level. Thus, genetic manipulation to inactivate PhoP-rv0805-cAMP pathway decreases cAMP level, stress tolerance, and intracellular survival of the bacillus.

Mycobacterium tuberculosis PhoP integrates stress response to intracellular survival by regulating cAMP level

Survival of Mycobacterium tuberculosis within the host macrophages requires the bacterial virulence regulator PhoP, but the underlying reason remains unknown. 3′,5′-Cyclic adenosine monophosphate (cAMP) is one of the most widely used second messengers, which impacts a wide range of cellular responses in microbial pathogens including M. tuberculosis. Herein, we hypothesized that intra-bacterial cAMP level could be controlled by PhoP since this major regulator plays a key role in bacterial responses against numerous stress conditions. A transcriptomic analysis reveals that PhoP functions as a repressor of cAMP-specific phosphodiesterase (PDE) Rv0805, which hydrolyzes cAMP. In keeping with these results, we find specific recruitment of the regulator within the promoter region of rv0805 PDE, and absence of phoP or ectopic expression of rv0805 independently accounts for elevated PDE synthesis, leading to the depletion of intra-bacterial cAMP level. Thus, genetic manipulation to inactivate PhoP-rv0805-cAMP pathway decreases cAMP level, stress tolerance, and intracellular survival of the bacillus.

Biocompatible plasma-treated liquids: A sustainable approach for decontaminating gastrointestinal-infection causing pathogens

Nosocomial infections are a serious threat and difficult to cure due to rising antibiotic resistance in pathogens and biofilms. Direct exposure to cold atmospheric plasma (CAP) has been widely employed in numerous biological research endeavors. Nonetheless, plasma-treated liquids (PTLs) formulated with physiological solutions may offer additional benefits such as enhanced portability, and biocompatibility. Additionally, CAP-infused long-lived reactive oxygen and nitrogen species (RONS) such as nitrite (NO2−), nitrate (NO3−), and hydrogen peroxide (H2O2) can synergistically induce their antibacterial activity. Herein, we investigated those argon-plasma jet-treated liquids, including Ringer’s lactate (RL), phosphate-buffered saline (PBS), and physiological saline, have significant antibacterial activity against nosocomial/gastrointestinal-causing pathogens, which might be due to ROS-mediated lipid peroxidation. Combining the conventional culture-based method with propidium iodide monoazide quantitative PCR (PMAxx™-qPCR) indicated that PTLs induce a minimal viable but non-culturable (VBNC) state and moderately affect culturable counts. Specifically, the PTL exposure resulted in pathogenicity dysfunction via controlling T3SS-related effector genes of S. enterica. Overall, this study provides insights into the effectiveness of PTLs for inducing ROS-mediated damage, controlling the virulence of diarrheagenic bacteria, and modulating homeostatic genes.

Establishment of Nested PCR for the Detection of Pseudomonas plecoglossicida and Epidemiological Survey of Larimichthys crocea in the Southeast Coastal Region

The visceral white nodules disease in the internal organs of Larimichthys crocea has caused significant harm in the aquaculture of this species, with Pseudomonas plecoglossicida considered one of the core pathogens causing this disease. In this study, we designed three pairs of specific nested PCR primers targeting the sctU gene of P. plecoglossicida, a crucial component of the Type III secretion system (T3SS), which is instrumental in bacterial pathogenesis and virulence. Through the optimization of PCR reaction conditions, specificity testing, and sensitivity determination, a method was established for the accurate detection of P. plecoglossicida. This method yielded single amplification products, exhibited a false positive rate of zero for reference bacteria, and achieved a detection sensitivity of a minimum of 2.62 copies/reaction for the target sequence. Using the detection method, we conducted analyses on the diseased populations of L. crocea, involving a total of 64 screened fishes along the southeast coast of China from 2021 to 2023. The results revealed that the infection rate of P. plecoglossicida in diseased L. crocea exceeded over 90% in March and April, while in other months, the maximum recorded infection rate was merely 10%. The detection method developed in this study shows potential for early warning and routine monitoring of visceral white nodules disease in the internal organs of species such as L. crocea.

Disrupting quorum sensing as a strategy to inhibit bacterial virulence in human, animal, and plant pathogens.

The development of sustainable alternatives to conventional antimicrobials is needed to address bacterial virulence while avoiding selecting resistant strains in a variety of fields, including human, animal and plant health. Quorum sensing (QS), a bacterial communication system involved in noxious bacterial phenotypes such as virulence, motility and biofilm formation, is of utmost interest. In this study, we harnessed the potential of the lactonase SsoPox to disrupt QS of human, fish, and plant pathogens. Lactonase treatment significantly alters phenotypes including biofilm formation, motility, and infection capacity. In plant pathogens, SsoPox decreased the production of plant cell wall degrading enzymes in Pectobacterium atrosepticum and reduced the maceration of onions infected by Burkholderia glumae. In human pathogens, lactonase treatment significantly reduced biofilm production in Acinetobacter baumannii, Burkholderia cepacia and Pseudomonas aeruginosa, with the cytotoxicity of the latter being reduced by SsoPox treatment. In fish pathogens, lactonase treatment inhibited biofilm formation and bioluminescence in Vibrio harveyi and affected QS regulation in Aeromonas salmonicida. QS inhibition can thus be used to largely impact the virulence of bacterial pathogens and would constitute a global and sustainable approach for public, crop and livestock health in line with the expectations of the One Health initiative.

Aquaculture and Aeromonas hydrophila: a complex interplay of environmental factors and virulence

AbstractAquaculture faces significant challenges due to bacterial pathogens like Aeromonas hydrophila, which can severely impact production and fish health. Understanding the relationship between environmental factors, host susceptibility, and bacterial virulence is crucial for effectively managing and mitigating the risks associated with A. hydrophila in aquaculture systems. A. hydrophila, found ubiquitously in aquatic environments, possesses various virulence factors that enhance its pathogenicity. These factors are closely linked to environmental conditions, such as temperature and pH, which play pivotal roles in bacterial growth, survival, and pathogenic potential. Fluctuations in temperature and pH significantly influence A. hydrophila’s metabolic activity and growth rate, thereby modulating its virulence and overall pathogenicity. Ammonia, a byproduct of aquatic organism metabolism and organic matter decomposition, can accumulate to toxic levels in aquaculture settings, compromising fish health and immune function. Elevated ammonia concentrations worsen A. hydrophila infections by compromising host immunity and creating favorable conditions for bacterial proliferation. Oxygen concentration, host signals, and diet formulation are significantly impacting the susceptibility of aquatic organisms to infection. These factors are the most crucial in shaping the ecology, physiology, and pathogenicity of A. hydrophila in aquaculture. There is limited information on how these environmental factors modulate the virulence genes of such important fish pathogens. The knowledge of A. hydrophila virulence and its interplay with environmental factors paves the way for developing strategies to prevent and control diseases in aquaculture.

Narrow spectrum nano-antibiotic for selective removal of ARB from contaminated water: New insights into stimuli response based on cellular attachment, lysis, and excretion

Narrow spectrum nano-antibiotics are supposedly the future trouble-shooters to improve the efficacy of conventional antimicrobials for treatment of severe bacterial infections, remove contamination from water and diminish the development of antibiotic resistance. In this study, antimicrobial peptide functionalized boron-carbon-nitride nanosheets ((Ant)pep@BCN NSs) are developed that are a promising wastewater disinfector and antibiotic resistant bactericide agent. These nanosheets are developed for selective removal and effective inactivation of antibiotic resistant bacteria (ARB) from water in presence of two virulent bacteria. The (Ant)pep@BCN NSs provide reactive surface receptors specific to the ARB. They mimic muralytic enzymes to damage the cell membrane of ARB. These NSs demonstrate 3-fold higher antimicrobial efficiency against the targeted ARB compared to pristine BCN even at lower concentrations. To the best of our knowledge, this is the first time that functionalized BCN has been developed to remove ARB selectively from wastewater. Furthermore, the (Ant)pep@BCN selectively reduced the microbiological load and led to morphological changes in Gram negative ARB in a mixed bacterial inoculum. These ARBs excreted outer–inner membrane vesicles (OIMVs) of triangular shape as a stimuli response to (Ant)pep@BCN NSs. These novel antimicrobial peptide-NSs have potential to improve treatment efficacy against ARB infections and water contamination.

Prophylactic efficacy of baicalin and carvacrol against Salmonella Typhimurium biofilm on food and food contact surfaces

This study examines the antimicrobial and antibiofilm effectiveness of baicalin and carvacrol against Salmonella enterica ser. Typhimurium on food contact surfaces and chicken meat. The minimum inhibitory concentrations (MIC) for baicalin and carvacrol were found to be 100 μg/mL and 200 μg/mL, respectively, which aligns with findings from previous studies. The compounds exhibited a concentration-dependent decrease in microbial populations and biofilm formation. When used together, they displayed a remarkable synergistic effect, greatly augmenting their antibacterial activity. The assessment of food quality demonstrated that these treatments have no negative impact on the sensory characteristics of chicken meat. The impact of the structure on biofilms was observed through the use of Field Emission Scanning Electron Microscopy (FE-SEM) and Confocal Laser Scanning Microscopy (CLSM), revealing disrupted biofilm architectures and decreased cell viability. Crucially, RT-PCR analysis revealed a marked downregulation of quorum sensing (luxS), virulence (hilA), and stress response (rpoS) genes, highlighting the multifaceted antimicrobial mechanism of action. This gene-specific suppression suggests a targeted disruption of bacterial communication and virulence pathways, offering insight into the comprehensive antibiofilm strategy. This provides further insight into the molecular mechanisms that contribute to their antibiofilm effects.

Multi-biological risk in groundwater-surface water system under landfill stress: Driven by bacterial size and biological toxicity

The variation in bacterial size and biotoxicity leads to different ecological risks. However, the diversity of bacterial size and virulence in bacterial communities has been neglected, leading to limitations and inaccuracies in risk assessment. Surface-subsurface interactions lead to the complexity, variability, and insidiousness of pathogen transmission in the environment. Mountainous landfills are considered as a major source of pathogens in subsurface systems. Although numerous studies have reported the geographic distribution of microbes in landfills, there is a lack of knowledge regarding the impacts on the microbial spatial distribution of bacterial size, which is a key factor affecting microbial migration and risks. In this study, the groundwater, river water, soil and leachate samples were collected inside and around a typical mountainous urban landfill, which is close to a river with a high hydraulic gradient and a strong surface–subsurface interaction. Small-sized (<0.2 μm) and large-sized (>0.2 μm) bacteria were separated to verify the variability of migration potential and spatial distribution of different sizes of bacteria in groundwater-surface water and soil, investigating the driving factors and accessing the biological risk of different sizes of bacteria. The results revealed notable differences in spatial distribution and driving factors among various bacterial sizes. Small-sized bacterial communities in groundwater and soils exhibited clear trends towards leachate along the water flow direction. In contrast, large-sized bacterial communities remained stable and resembled native bacterial communities. Groundwater hydrodynamics was the main driving force affecting the spatial distribution of small-sized bacteria. The small-sized bacteria showed a higher content of virulence genes which were predominantly expressed for invasion. Thus, small-sized bacteria exhibited a stronger migration potential and a higher biological risk. Due to the surface–subsurface interactions, the bacterial communities in river water were more similar to that in groundwater after rain. Our results provide strong support to guide the management of subsurface system safety in mountainous landfills.

Intracellular Protective Functions and Therapeutical Potential of Trehalose.

Trehalose is a naturally occurring, non-reducing saccharide widely distributed in nature. Over the years, research on trehalose has revealed that this initially thought simple storage molecule is a multifunctional and multitasking compound protecting cells against various stress factors. This review presents data on the role of trehalose in maintaining cellular homeostasis under stress conditions and in the virulence of bacteria and fungi. Numerous studies have demonstrated that trehalose acts in the cell as an osmoprotectant, chemical chaperone, free radical scavenger, carbon source, virulence factor, and metabolic regulator. The increasingly researched medical and therapeutic applications of trehalose are also discussed.

Generation of specific immune memory by bacterial exposure in the major malaria vector Anopheles arabiensis (Diptera: Culicidae)

There is a growing body of evidence that invertebrates can generate improved secondary responses after a primary challenge. This immunological memory can be primed by a range of pathogens, including bacteria. The generation of immunological memory has been demonstrated in mosquitoes, with the memory primed by a range of initial stimuli. This study aimed to examine whether insecticide resistance affects the capacity to generate immunological memory. The primary hypothesis was tested by examining the capacity of genetically related laboratory-reared Anopheles arabiensis strains that differ by insecticide resistant phenotype to generate immunological memory. The competing hypothesis tested was that the bacterial virulence was the key determinant in generating immunological memory. Immune memory was generated in F1 females but not males. Immunological memory was demonstrated in both laboratory strains, but the efficacy differed by the insecticide resistant phenotype of the strain. An initial oral challenge provided by a blood meal resulted generated better memory than an oral challenge by sugar. The efficacy of memory generation between the two bacterial strains differed between the two mosquito strains. Regardless of the challenge, the two strains differed in their capacity to generate memory. This study therefore demonstrated that insecticide resistant phenotype affected the capacity of the two strains to generate immunological memory. Although this study needs to be replicated with wild mosquitoes, it does suggest that a potential role for insecticide resistance in the functioning of the immune system and memory generation of An. arabiensis.

Resistance to bacteriophage incurs a cost to virulence in drug-resistant Acinetobacter baumannii.

Introduction . Acinetobacter baumannii is a critical priority pathogen for novel antimicrobials (World Health Organization) because of the rise in nosocomial infections and its ability to evolve resistance to last resort antibiotics. A. baumannii is thus a priority target for phage therapeutics. Two strains of a novel, virulent bacteriophage (LemonAid and Tonic) able to infect carbapenem-resistant A. baumannii (strain NCTC 13420), were isolated from environmental water samples collected through a citizen science programme.Gap statement. Phage-host coevolution can lead to emergence of host resistance, with a concomitant reduction in the virulence of host bacteria; a potential benefit to phage therapy applications.Methodology. In vitro and in vivo assays, genomics and microscopy techniques were used to characterize the phages; determine mechanisms and impact of phage resistance on host virulence, and the efficacy of the phages against A. baumannii.Results. A. baumannii developed resistance to both viruses, LemonAid and Tonic. Resistance came at a cost to virulence, with the resistant variants causing significantly reduced mortality in a Galleria mellonella larval in vivo model. A replicated 8 bp insertion increased in frequency (~40 % higher frequency than in the wild-type) within phage-resistant A. baumannii mutants, putatively resulting in early truncation of a protein of unknown function. Evidence from comparative genomics and an adsorption assay suggests this protein acts as a novel phage receptor site in A. baumannii. We find no evidence linking resistance to changes in capsule structure, a known virulence factor. LemonAid efficiently suppressed growth of A. baumanni in vitro across a wide range of titres. However, in vivo, while survival of A. baumannii infected larvae significantly increased with both remedial and prophylactic treatment with LemonAid (107 p.f.u. ml-1), the effect was weak and not sufficient to save larvae from morbidity and mortality.Conclusion. While LemonAid and Tonic did not prove effective as a treatment in a Galleria larvae model, there is potential to harness their ability to attenuate virulence in drug-resistant A. baumannii.

GHK-Cu/Pionin-loaded in situ electrospun PVB/PVP smart dressing promotes wound healing via anti-oxidant, anti-inflammatory, antimicrobial, and tissue regenerative effects

Biocompatible, antibacterial, anti-inflammatory, and tissue regenerative smart dressings are in urgent need for infected skin wound repair in clinics. Portable in situ 3D-electrospun technology has the great advantage of direct deposition of required smart dressing on wound surfaces. Here, we fabricated a copper peptide (GHK-Cu) and quaternium-73 (Pionin) dual-drug-loaded polyvinyl butyral (PVB)/polyvinylpyrrolidone (PVP) smart nanofibers dressing using in-situ electrospinning technology for skin wound repair. The physicochemical properties and biological activities of smart dressing were extensively analyzed. In vivo biocompatibility, anti-oxidant, anti-inflammatory, and antimicrobial activities of smart dressing were analyzed during wound healing. Stable and homogeneous PVB/PVP nanofiber smart dressing with uniformly distributed GHK-Cu and Pionin and anabolic biological activities was obtained. Biocompatible smart dressing gave a sustained release of GHK-Cu and Pionin, promoted the migration and adhesion of dermal fibroblasts and keratinocytes, and showed anti-oxidant and anti-apoptotic effects in vitro and in vivo. Smart dressing exerted anti-inflammatory properties via M1 to M2 macrophage phenotype switching and effectively promoted wound healing. Pionin released from smart dressing not only killed but also inhibited the expression and delivery of virulence factor expression and bacteria adhesion. During wound healing, smart dressing promoted the proliferation of cells in the epidermal tissue, epithelial tissue remodeling, granulation tissue growth, neovascularization, and M2 macrophage polarization. Moreover, this smart dressing scavenged excess reactive oxygen species, increased SOD3 and SIRT1 expression, and repaired peroxidized tissue, consequently promoting wound healing. In summary, our results indicate that GHK-Cu/Pionin-loaded in situ electrospun PVB/PVP smart dressing promotes wound healing via antioxidant, anti-inflammatory, antimicrobial, and tissue regenerative effects, suggesting clinical application of this smart dressing for complicated skin wound healing.

Novel insights into the inhibitory effect of pterostilbene targeting Aeromonas hydrophila virulence

The overuse of antibiotics in aquaculture brings a range of problems. Therefore, novel approaches alternating antibiotics are urgently needed. Strategies targeting bacterial virulence have become one of the routes developing drugs against bacterial infections. Here, we found that pterostilbene (PSE) could inhibit the activity of aerolysin (AerA) and disrupt quorum sensing (QS) at sub-inhibitory concentrations. Molecular docking and dynamics simulation assays were performed to predict the binding mode and binding sites of AerA-PSE complex. Then we confirmed that PSE bound to the sites of Val189 and Ile302 and prevented AerA forming heptamer with transmembrane pores. In addition, PSE could protect to A549 cells and the channel catfish (Ictalurus punctatus) against AerA mediated cell injury and mortality infected with A. hydrophila. The findings demonstrated that targeting bacterial virulence could be a promising measure identifying agents against A. hydrophila infections.

Bacterial Sphingolipids Exacerbate Colitis by Inhibiting ILC3-derived IL-22 Production.

Gut bacterial sphingolipids, primarily produced by Bacteroidetes, have dual roles as bacterial virulence factors and regulators of the host mucosal immune system, including regulatory T cells and iNKT cells. IBD patients display altered sphingolipids profiles in fecal samples. However, how bacterial sphingolipids modulate mucosal homeostasis and regulate intestinal inflammation remains unclear. We utilized DSS-induced colitis in mice mono-colonized with Bacteroides fragilis strains expressing or lacking sphingolipids to assess the influence of bacterial sphingolipids on intestinal inflammation employing transcriptional, protein, and cellular analyses. Colonic explant and organoid were used to study the function of bacterial sphingolipids. Host mucosal immune cells and cytokines were profiled and characterized using flow cytometry, ELISA, and Western Blot, and cytokine function in vivo was investigated by monoclonal antibody injection. B. fragilis sphingolipids exacerbated intestinal inflammation. Mice mono-colonized with B. fragilis lacking sphingolipids exhibited less severe DSS-induced colitis. This amelioration of colitis was associated with increased production of interleukin-22 by ILC3. Mice colonized with B. fragilis lacking sphingolipids following DSS treatment showed enhanced epithelial STAT3 activity, intestinal cell proliferation, and antimicrobial peptide production. Protection against DSS colitis associated with B. fragilis lacking sphingolipids was reversed upon IL-22 blockade. Furthermore, bacterial sphingolipids restricted epithelial IL-18 production following DSS treatment and interfered with IL-22 production by a subset of ILC3 cells expressing both IL-18R and MHC II. B. fragilis-derived sphingolipids exacerbate mucosal inflammation by impeding epithelial IL-18 expression and concomitantly suppressing the production of IL-22 by ILC3 cells.

A potential virulence factor: Brucella flagellin FliK does not affect the main biological properties but inhibits the inflammatory response in RAW264.7 cells

The bacterial flagellum is an elongated filament that protrudes from the cell and is responsible for bacterial motility. It can also be a pathogen-associated molecular pattern (PAMP) that regulates the host immune response and is involved in bacterial pathogenicity. In contrast to motile bacteria, the Brucella flagellum does not serve a motile purpose. Instead, it plays a role in regulating Brucella virulence and the host‘s immune response, similar to other non-motile bacteria. The flagellin protein, FliK, plays a key role in assembly of the flagellum and also as a potential virulence factor involved in the regulation of bacterial virulence and pathogenicity. In this study, we generated a Brucella suis S2 flik gene deletion strain and its complemented strain and found that deletion of the flik gene has no significant effect on the main biological properties of Brucella, but significantly enhanced the inflammatory response induced by Brucella infection of RAW264.7 macrophages. Further experiments demonstrated that the FliK protein was able to inhibit LPS-induced cellular inflammatory responses by down-regulating the expression of MyD88 and NF-κB, and by decreasing p65 phosphorylation in the NF-κB pathway; it also inhibited the expression of NLRP3 and caspase-1 in the NLRP3 inflammasome pathway. In conclusion, our study suggests that Brucella FliK may act as a virulence factor involved in the regulation of Brucella pathogenicity and modulation of the host immune response.

Cell wall-mediated root development is targeted by a soil-borne bacterial pathogen to promote infection

Plant pathogens manipulate host development, facilitating colonization and proliferation. Ralstonia solanacearum is a soil-borne bacterial pathogen that penetrates roots and colonizes plants through the vascular system, causing wilting and death. Here, we find that RipAC, an effector protein from R.solanacearum, alters root development in Arabidopsis, promoting the formation of lateral roots and root hairs. RipAC interacts with CELLULOSE SYNTHASE (CESA)-INTERACTIVE PROTEIN 1 (CSI1), which regulates the activity of CESA complexes at the plasma membrane. RipAC disrupts CESA-CSI1 interaction, leading to a reduction in cellulose content, root developmental alterations, and a promotion of bacterial pathogenicity. We find that CSI1 also associates with the receptor kinase FERONIA, forming a complex that negatively regulates immunity in roots; this interaction, however, is not affected by RipAC. Our work reveals a bacterial virulence strategy that selectively affects the activities of a host target, promoting anatomical alterations that facilitate infection without causing activation of immunity.

Community-acquired Klebsiella pneumoniae pneumonia in ICU: a multicenter retrospective study

BackgroundAlongside the recent worldwide expansion of hypervirulent Klebsiella pneumoniae (KP) infections, the available literature regarding cases of community acquired pneumonias (KP-CAP) remains scarce but reports a strikingly high and early mortality. We performed a retrospective multicenter study (7 ICU in France) between 2015 and 2019, comparing prognosis and severity of KP-CAP versus Streptococcus pneumoniae - CAP (SP-CAP).MethodsFor each KP-CAP, three SP-CAP admitted in ICUs within the same center and within the same 6-month window were selected. When available, KP strains were studied, and bacterial virulence was genetically assessed for virulence factors. The primary outcome was in-hospital mortality. Associations between clinical outcomes and type of infection were tested using univariate and multivariate logistic regressions, adjusted for pairing variables.ResultsTwenty-seven KP-CAP and 81 SP-CAP were included. Respective in-hospital mortality rates were 59% (n = 16) and 17% (n = 14, p < 0.001), despite adequate antibiotic therapy. KP-CAP median time from admission to death was 26.9 h [IQR 5.75–44 h] and were significantly associated with higher rates of multiple organ failures (93% vs. 42%, p < 0.001), disseminated intravascular coagulation (12% vs. 1.3%, p = 0.046), septic shock (median lactate on ICU admission 4.60 vs. 2.90 mmol/L, p = 0.030) and kidney failure (KDIGO-3: 87% vs. 44%, p < 0.001). Interestingly, alcoholism was the only identified predisposing factor of KP-CAP. Severity on ICU admission (2-fold higher for KP-CAP) was the only factor associated with mortality in a multivariate analysis.ConclusionWe described a strong association between KP-CAP infection and higher and earlier mortality when compared to SP-CAP. Moreover, alcoholism was the sole predisposing factor associated with KP-CAP infection. These findings should raise awareness of clinicians involved in the management of severe CAP about this microbiological etiology. Future prospective studies are needed to confirm these results and to design strategies to improve the prognosis of such infections.

Exploring Immune Redox Modulation in Bacterial Infections: Insights into Thioredoxin-Mediated Interactions and Implications for Understanding Host–Pathogen Dynamics

Exploring Immune Redox Modulation in Bacterial Infections: Insights into Thioredoxin-Mediated Interactions and Implications for Understanding Host–Pathogen Dynamics