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477000.9068Whole-genome sequencing of bacteria accountable for lactational mastitis in humans combined with an examination of their antibiotic resistance profiles. Lactational mastitis, a common condition affecting nursing mothers, is characterized by mammary gland inflammation during lactation. This inflammatory response typically occurs due to bacterial infection. The discomfort and pain associated with lactational mastitis can significantly impact a mother's ability to breastfeed comfortably and may lead to the cessation of breastfeeding altogether if left untreated. Antibiotics are commonly prescribed to target the bacteria causing the infection and alleviate symptoms, aiming to treat the infection. Nevertheless, a notable worry linked to antibiotic use is the emergence of antibiotic resistance, compounded by the possible persistence of antibiotics in milk. Additionally, lactational mastitis is characterized by its polymicrobial nature. In this study, bacteria were isolated from infected breast milk samples and whole-genome sequencing was performed on eleven isolates to accurately identify the bacteria and assess their antibiotic resistance profiles. Using Galaxy tools and the ResFinder database, we identified Bacillus paraanthracis, Bacillus altitudinis, Staphylococcus aureus, Bacillus cereus, Escherichia coli, Alcaligenes faecalis, and Bacillus licheniformis, along with antibiotic-resistant genes like fosB1, cat86, erm (D), blaZ, and mdf (A). ABRicate aided in antimicrobial resistance (AMR) gene analysis, and CARD visualized their distribution. Our study demonstrates that the severity of infection is directly proportional to an increase in somatic cell count (SCC). This research sheds light on microbial diversity in lactational mastitis milk and provides crucial insights into antibiotic-resistance genes. Utilizing bioinformatics tools, such as those employed in this study, can inform the design of effective treatment strategies for lactational mastitis infections.202439320640
61110.8986The Staphylococcus aureus FASII bypass escape route from FASII inhibitors. Antimicrobials targeting the fatty acid synthesis (FASII) pathway are being developed as alternative treatments for bacterial infections. Emergence of resistance to FASII inhibitors was mainly considered as a consequence of mutations in the FASII target genes. However, an alternative and efficient anti-FASII resistance strategy, called here FASII bypass, was uncovered. Bacteria that bypass FASII incorporate exogenous fatty acids in membrane lipids, and thus dispense with the need for FASII. This strategy is used by numerous Gram-positive low GC % bacteria, including streptococci, enterococci, and staphylococci. Some bacteria repress FASII genes once fatty acids are available, and "constitutively" shift to FASII bypass. Others, such as the major pathogen Staphylococcus aureus, can undergo high frequency mutations that favor FASII bypass. This capacity is particularly relevant during infection, as the host supplies the fatty acids needed for bacteria to bypass FASII and thus become resistant to FASII inhibitors. Screenings for anti-FASII resistance in the presence of exogenous fatty acids confirmed that FASII bypass confers anti-FASII resistance among clinical and veterinary isolates. Polymorphisms in S. aureus FASII initiation enzymes favor FASII bypass, possibly by increasing availability of acyl-carrier protein, a required intermediate. Here we review FASII bypass and consequences in light of proposed uses of anti-FASII to treat infections, with a focus on FASII bypass in S. aureus.201728728970
864220.8963Dynamics of Thioalkalivibrio species in a co-culture under selective pressure of ampicillin. Haloalkaliphilic chemolithoautotrophic sulfur-oxidizing bacteria belonging to the genus Thioalkalivibrio are highly abundant in microbial communities found in soda lakes and dominant in full-scale bioreactors removing sulfide from industrial waste gases. Despite certain soda lakes being remote and unaffected by anthropogenic activities, haloalkaliphilic microorganisms, including Thioalkalivibrio strains, possess various antibiotic resistance genes. In this study, we investigated the impact of the antibiotic ampicillin on a co-culture of two Thioalkalivibrio species, Tv. thiocyanoxidans ARh2(T) and Tv. versutus AL2(T), both experimentally and through in silico analysis of antibiotic resistance. Cell growth dynamics were monitored over time at increasing ampicillin concentrations using rep- and qPCR. Within ten days after the addition of ampicillin, the co-culture transitioned from a Tv. thiocyanoxidans ARh2(T)-dominated to a stable Tv. versutus AL2(T)-dominated culture. This shift was attributed to Tv. versutus AL2(T) displaying a lower susceptibility to ampicillin, making it more competitive. These results emphasize the potential implications of antibiotic pressure on microbial communities, where a resistant species can outcompete a stable co-culture. This study presents the first evidence of such dynamics in haloalkaliphilic chemolithoautotrophs. By understanding the antibiotic resistance and the competitive dynamics of haloalkaliphilic bacteria like Thioalkalivibrio, we can gain insights into their behaviour and stress response.202338077120
62030.8962Transcriptomic Responses and Survival Mechanisms of Staphylococci to the Antimicrobial Skin Lipid Sphingosine. Sphingosines are antimicrobial lipids that form part of the innate barrier to skin colonization by microbes. Sphingosine deficiencies can result in increased epithelial infections by bacteria including Staphylococcus aureus. Recent studies have focused on the potential use of sphingosine resistance or its potential mechanisms. We used RNA-Seq to identify the common d-sphingosine transcriptomic response of the transient skin colonizer S. aureus and the dominant skin coloniser S. epidermidis. A common d-sphingosine stimulon was identified that included downregulation of the SaeSR two-component system (TCS) regulon and upregulation of both the VraSR TCS and CtsR stress regulons. We show that the PstSCAB phosphate transporter, and VraSR offer intrinsic resistance to d-sphingosine. Further, we demonstrate increased sphingosine resistance in these staphylococci evolves readily through mutations in genes encoding the FarE-FarR efflux/regulator proteins. The ease of selecting mutants with resistance to sphingosine may impact upon staphylococcal colonization of skin where the lipid is present and have implications with topical therapeutic applications.202234902269
906340.8961Role of Oral Bacteria in Mediating Gemcitabine Resistance in Pancreatic Cancer. Oral microbiota have been implicated in pancreatic ductal adenocarcinoma (PDAC) and may contribute to chemotherapy resistance. While previous studies attributed bacteria-induced resistance to indirect host modulation, recent findings suggest a direct mechanism. Escherichia coli expressing long-form cytidine deaminase (CDD(L)) can degrade gemcitabine, a chemotherapeutic agent, into a non-toxic form, leading to resistance. In contrast, bacteria carrying short form (CDD(S)) or lacking CDD did not induce resistance. This study investigates whether oral bacteria can cause gemcitabine resistance in PDAC cells through CDD-mediated degradation. Oral microbes associated with PDAC were selected based on CDD isoforms: Aggregatibacter actinomycetemcomitans carrying CDD(L), Enterococcus faecalis, Streptococcus mutans, Porphyromonas gingivalis, all carrying CDD(S), and Fusobacterium nucleatum lacking CDD. The selected microbes, along with wild-type and CDD-deficient E. coli, were co-incubated with gemcitabine to assess its degradation and PDAC cell proliferation. A. actinomycetemcomitans fully degraded gemcitabine and induced resistance. Surprisingly, CDD(S)-expressing oral bacteria partially degraded gemcitabine in a strain-dependent manner. Expressing either CDD(L) or CDD(S) in CDD-deficient E. coli resulted in equivalent gemcitabine degradation and resistance, indicating that CDD function is independent of isoform length. These findings highlight the role of oral bacteria in gemcitabine resistance and the need for strategies to mitigate microbial-driven resistance in PDAC treatment.202540723890
906550.8957Gut Bacteria Promote Phosphine Susceptibility of Tribolium castaneum by Aggravating Oxidative Stress and Fitness Costs. Knowledge about resistance mechanisms can provide ideas for pesticide resistance management. Although several studies have unveiled the positive or negative impacts of gut microbes on host pesticide resistance, minimal research is available regarding the association between gut microbes and host phosphine resistance. To explore the influence of gut bacteria on host phosphine susceptibility and its molecular basis, mortality, fitness, redox responses, and immune responses of adult Tribolium castaneum were determined when it was challenged by phosphine exposure and/or gut bacteria inoculation. Five cultivable gut bacteria were excised from a population of phosphine-resistant T. castaneum. Among them, only Enterococcus sp. inoculation significantly promoted host susceptibility to phosphine, while inoculation of any other gut bacteria had no significant effect on host phosphine susceptibility. Furthermore, when T. castaneum was exposed to phosphine, Enterococcus sp. inoculation decreased the female fecundity, promoted host oxidative stress, and suppressed the expression and activity of host superoxide dismutase, catalase, and peroxidase. In the absence of phosphine, Enterococcus sp. inoculation also elicited overactive immune responses in T. castaneum, including the immune deficiency and Toll signaling pathways and the dual oxidase-reactive oxygen species system. These results indicate that Enterococcus sp. likely promotes host phosphine susceptibility by aggravating oxidative stress and fitness costs.202337887827
81160.8956Genomic analysis of five antibiotic-resistant bacteria isolated from the environment. Our study presents the whole-genome sequences and annotation of five bacteria isolates, each demonstrating distinct antibiotic resistance. These isolates include Bacillus paranthracis RIT 841, Atlantibacter hermanii RIT 842, Pantoea leporis RIT 844, Enterococcus casseliflavus RIT 845, and Pseudomonas alkylphenolica RIT 846, underscoring the importance of understanding antimicrobial resistance.202439189722
61970.8954Inactivation of farR Causes High Rhodomyrtone Resistance and Increased Pathogenicity in Staphylococcus aureus. Rhodomyrtone (Rom) is an acylphloroglucinol antibiotic originally isolated from leaves of Rhodomyrtus tomentosa. Rom targets the bacterial membrane and is active against a wide range of Gram-positive bacteria but the exact mode of action remains obscure. Here we isolated and characterized a spontaneous Rom-resistant mutant from the model strain Staphylococcus aureus HG001 (Rom(R)) to learn more about the resistance mechanism. We showed that Rom-resistance is based on a single point mutation in the coding region of farR [regulator of fatty acid (FA) resistance] that causes an amino acid change from Cys to Arg at position 116 in FarR, that affects FarR activity. Comparative transcriptome analysis revealed that mutated farR affects transcription of many genes in distinct pathways. FarR represses for example the expression of its own gene (farR), its flanking gene farE (effector of FA resistance), and other global regulators such as agr and sarA. All these genes were consequently upregulated in the Rom(R) clone. Particularly the upregulation of agr and sarA leads to increased expression of virulence genes rendering the Rom(R) clone more cytotoxic and more pathogenic in a mouse infection model. The Rom-resistance is largely due to the de-repression of farE. FarE is described as an efflux pump for linoleic and arachidonic acids. We observed an increased release of lipids in the Rom(R) clone compared to its parental strain HG001. If farE is deleted in the Rom(R) clone, or, if native farR is expressed in the Rom(R) strain, the corresponding strains become hypersensitive to Rom. Overall, we show here that the high Rom-resistance is mediated by overexpression of farE in the Rom(R) clone, that FarR is an important regulator, and that the point mutation in farR (Rom(R) clone) makes the clone hyper-virulent.201931191485
323080.8953Effect of large-scale population-based dietary change to vegetarianism on antimicrobial resistance and bacterial composition of sewage in Thailand. Antimicrobial resistance (AMR) is on one of the global priority challenges. This study explored the impact of diet alteration on AMR bacteria through metagenomic analysis during the annual vegetarian festival in Thailand in October 2019. The study investigated the effects of a 10-day shift from a regular to a vegetarian diet by collecting urban sewage from Nakhon Sawan, Surat Thani, and Bangkok before, during, and after the festival. Additionally, faecal samples from individuals in the northern city were analyzed. Using shotgun metagenomic sequencing, the samples were mapped against bacterial, AMR genes, and carbohydrate-active enzymes databases. The results revealed significant changes in AMR gene abundance and increased carbohydrate metabolism genes in sewage samples from all three cities during the festival. There was also a notable shift in the composition and diversity of bacterial species, particularly in the northern city. The total abundance of AMR genes increased during the vegetarian festival across all locations. This study highlights the correlation between a population's vegetarian diet and increased AMR in Thailand. It also demonstrates that metagenomic analysis of sewage can effectively assess the impact of dietary changes on bacterial communities and AMR at a population level, providing valuable insights for public health strategies.202540389018
19290.8951N-Succinyltransferase Encoded by a Cryptic Siderophore Biosynthesis Gene Cluster in Streptomyces Modifies Structurally Distinct Antibiotics. The antibiotic desertomycin A and its previously undescribed inactive N-succinylated analogue, desertomycin X, were isolated from Streptomyces sp. strain YIM 121038. Genome sequencing and analysis readily identified the desertomycin biosynthetic gene cluster (BGC), which lacked genes encoding acyltransferases that would account for desertomycin X formation. Scouting the genome for putative N-acyltransferase genes led to the identification of a candidate within a cryptic siderophore BGC (csb) encoding a putative homologue of the N6'-hydroxylysine acetyltransferase IucB. Expression of the codon-optimized gene designated csbC in Escherichia coli yielded the recombinant protein that was able to N-succinylate desertomycin A as well as several other structurally distinct antibiotics harboring amino groups. Some antibiotics were rendered antibiotically inactive due to the CsbC-catalyzed succinylation in vitro. Unlike many known N-acyltransferases involved in antibiotic resistance, CsbC could not efficiently acetylate the same antibiotics. When expressed in E. coli, CsbC provided low-level resistance to kanamycin and ampicillin, suggesting that it may play a role in antibiotic resistance in natural habitats, where the concentration of antibiotics is usually low. IMPORTANCE In their natural habitats, bacteria encounter a plethora of organic compounds, some of which may be represented by antibiotics produced by certain members of the microbial community. A number of antibiotic resistance mechanisms have been described, including those specified by distinct genes encoding proteins that degrade, modify, or expel antibiotics. In this study, we report identification and characterization of an enzyme apparently involved in the biosynthesis of a siderophore, but also having the ability of modify and thereby inactivate a wide variety of structurally diverse antibiotics. This discovery sheds light on additional capabilities of bacteria to withstand antibiotic treatment and suggests that enzymes involved in secondary metabolism may have an additional function in the natural environment.202236040031
615100.8950Escherichia coli RclA is a highly active hypothiocyanite reductase. Hypothiocyanite and hypothiocyanous acid (OSCN(-)/HOSCN) are pseudohypohalous acids released by the innate immune system which are capable of rapidly oxidizing sulfur-containing amino acids, causing significant protein aggregation and damage to invading bacteria. HOSCN is abundant in saliva and airway secretions and has long been considered a highly specific antimicrobial that is nearly harmless to mammalian cells. However, certain bacteria, commensal and pathogenic, are able to escape damage by HOSCN and other harmful antimicrobials during inflammation, which allows them to continue to grow and, in some cases, cause severe disease. The exact genes or mechanisms by which bacteria respond to HOSCN have not yet been elucidated. We have found, in Escherichia coli, that the flavoprotein RclA, previously implicated in reactive chlorine resistance, reduces HOSCN to thiocyanate with near-perfect catalytic efficiency and strongly protects E. coli against HOSCN toxicity. This is notable in E. coli because this species thrives in the chronically inflamed environment found in patients with inflammatory bowel disease and is able to compete with and outgrow other important commensal organisms, suggesting that HOSCN may be a relevant antimicrobial in the gut, which has not previously been explored. RclA is conserved in a variety of epithelium-colonizing bacteria, implicating its HOSCN reductase activity in a variety of host-microbe interactions. We show that an rclA mutant of the probiotic Limosilactobacillus reuteri is sensitive to HOSCN and that RclA homologs from Staphylococcus aureus, Streptococcus pneumoniae, and Bacteroides thetaiotaomicron all have potent protective activity against HOSCN when expressed in E. coli.202235867824
9996110.8948In Situ Localization of Staphylococcus shinii and Staphylococcus succinus in Infected Rhipicephalus microplus Ticks: Implications for Biocontrol Strategies. Rhipicephalus microplus is a blood-sucking parasite that causes heavy infestations on cattle and is a vector for severe tick-borne diseases, such as anaplasmosis and babesiosis, and poses a significant threat to the cattle industry. Cattle ticks show increasing acaricide resistance, which creates an additional problem concerning the inefficient chemical control of tick populations in cattle-grazing areas, necessitating the exploration of alternative tick biocontrol methods. Our study aimed to demonstrate the acaropathogenic efficacy of two bacterial species during experimental infections on R. microplus. Our experimental data confirmed that S. shinii and S. succinus exhibited significant acaropathogenic properties against R. microplus, as demonstrated by the tracking of fluorescent-labeled bacteria within the engorged-tick body. Our experiments revealed that both bacterial species could infect the hemolymph, salivary glands, and vestibular vagina of the tick, inducing histological changes in the affected organs that may impair feeding as well as reproductive capabilities. Gené's organ infection was detected only in S. succinus. Our findings offer valuable insights for developing biocontrol strategies to manage Rhipicephalus microplus populations effectively.202439770285
235120.8945Effect of Application of Probiotic Pollen Suspension on Immune Response and Gut Microbiota of Honey Bees (Apis mellifera). Although the use of probiotic bacteria in invertebrates is still rare, scientists have begun to look into their usage in honey bees. The probiotic preparation, based on the autochthonous strain Lactobacillus brevis B50 Biocenol™ (CCM 8618), which was isolated from the digestive tracts of healthy bees, was applied to the bee colonies in the form of a pollen suspension. Its influence on the immune response was determined by monitoring the expression of genes encoding immunologically important molecules in the honey bee intestines. Changes in the intestinal microbiota composition were also studied. The results showed that the probiotic Lact. brevis B50, on a pollen carrier, significantly increased the expression of genes encoding antimicrobial peptides (abaecin, defensin-1) as well as pattern recognition receptors (toll-like receptor, peptidoglycan recognition proteins). Gene expression for the other tested molecules included in Toll and Imd signaling pathways (dorsal, cactus, kenny, relish) significantly changed during the experiment. The positive effect on intestinal microbiota was manifested mainly by a significant increase in the ratio of lactic acid bacteria to enterobacteria. These findings confirm the potential of the tested probiotic preparation to enhance immunity in bee colonies and thus increase their resistance to infectious diseases and stress conditions.202031912341
616130.8944Identification of lipoteichoic acid as a ligand for draper in the phagocytosis of Staphylococcus aureus by Drosophila hemocytes. Phagocytosis is central to cellular immunity against bacterial infections. As in mammals, both opsonin-dependent and -independent mechanisms of phagocytosis seemingly exist in Drosophila. Although candidate Drosophila receptors for phagocytosis have been reported, how they recognize bacteria, either directly or indirectly, remains to be elucidated. We searched for the Staphylococcus aureus genes required for phagocytosis by Drosophila hemocytes in a screening of mutant strains with defects in the structure of the cell wall. The genes identified included ltaS, which encodes an enzyme responsible for the synthesis of lipoteichoic acid. ltaS-dependent phagocytosis of S. aureus required the receptor Draper but not Eater or Nimrod C1, and Draper-lacking flies showed reduced resistance to a septic infection of S. aureus without a change in a humoral immune response. Finally, lipoteichoic acid bound to the extracellular region of Draper. We propose that lipoteichoic acid serves as a ligand for Draper in the phagocytosis of S. aureus by Drosophila hemocytes and that the phagocytic elimination of invading bacteria is required for flies to survive the infection.200919890048
8188140.8943Biofilm in implant infections: its production and regulation. A significant proportion of medical implants become the focus of a device-related infection, difficult to eradicate because bacteria that cause these infections live in well-developed biofilms. Biofilm is a microbial derived sessile community characterized by cells that are irreversibly attached to a substratum or interface to each other, embedded in a matrix of extracellular polymeric substances that they have produced. Bacterial adherence and biofilm production proceed in two steps: first, an attachment to a surface and, second, a cell-to-cell adhesion, with pluristratification of bacteria onto the artificial surface. The first step requires the mediation of bacterial surface proteins, the cardinal of which is similar to S. aureus autolysin and is denominated AtlE. In staphylococci the matrix of extracellular polymeric substances of biofilm is a polymer of beta-1,6-linked N-acetylglucosamine (PIA), whose synthesis is mediated by the ica operon. Biofilm formation is partially controlled by quorum sensing, an interbacterial communication mechanism dependent on population density. The principal implants that can be compromised by biofilm associated infections are: central venous catheters, heart valves, ventricular assist devices, coronary stents, neurosurgical ventricular shunts, implantable neurological stimulators, arthro-prostheses, fracture-fixation devices, inflatable penile implants, breast implants, cochlear implants, intraocular lenses, dental implants. Biofilms play an important role in the spread of antibiotic resistance. Within the high dense bacterial population, efficient horizontal transfer of resistance and virulence genes takes place. In the future, treatments that inhibit the transcription of biofilm controlling genes might be a successful strategy in inhibiting these infections.A significant proportion of medical implants become the focus of a device-related infection, difficult to eradicate because bacteria that cause these infections live in well-developed biofilms. Biofilm is a microbial derived sessile community characterized by cells that are irreversibly attached to a substratum or interface to each other, embedded in a matrix of extracellular polymeric substances that they have produced. Bacterial adherence and biofilm production proceed in two steps: first, an attachment to a surface and, second, a cell-to-cell adhesion, with pluristratification of bacteria onto the artificial surface. The first step requires the mediation of bacterial surface proteins, the cardinal of which is similar to S. aureus autolysin and is denominated AtlE. In staphylococci the matrix of extracellular polymeric substances of biofilm is a polymer of beta-1,6-linked N-acetylglucosamine (PIA), whose synthesis is mediated by the ica operon. Biofilm formation is partially controlled by quorum sensing, an interbacterial communication mechanism dependent on population density. The principal implants that can be compromised by biofilm associated infections are: central venous catheters, heart valves, ventricular assist devices, coronary stents, neurosurgical ventricular shunts, implantable neurological stimulators, arthro-prostheses, fracture-fixation devices, inflatable penile implants, breast implants, cochlear implants, intra-ocular lenses, dental implants. Biofilms play an important role in the spread of antibiotic resistance. Within the high dense bacterial population, efficient horizontal transfer of resistance and virulence genes takes place. In the future, treatments that inhibit the transcription of biofilm controlling genes might be a successful strategy in inhibiting these infections.200516353112
118150.8943Trichlorination of a Teicoplanin-Type Glycopeptide Antibiotic by the Halogenase StaI Evades Resistance. Glycopeptide antibiotics (GPAs) include clinically important drugs used for the treatment of infections caused by Gram-positive pathogens. These antibiotics are specialized metabolites produced by several genera of actinomycete bacteria. While many GPAs are highly chemically modified, A47934 is a relatively unadorned GPA lacking sugar or acyl modifications, common to other members of the class, but which is chlorinated at three distinct sites. The biosynthesis of A47934 is encoded by a 68-kb gene cluster in Streptomyces toyocaensis NRRL 15009. The cluster includes all necessary genes for the synthesis of A47934, including two predicted halogenase genes, staI and staK In this study, we report that only one of the halogenase genes, staI, is necessary and essential for A47934 biosynthesis. Chlorination of the A47934 scaffold is important for antibiotic activity, as assessed by binding affinity for the target N-acyl-d-Ala-d-Ala. Surprisingly, chlorination is also vital to avoid activation of enterococcal and Streptomyces VanB-type GPA resistance through induction of resistance genes. Phenotypic assays showed stronger induction of GPA resistance by the dechlorinated compared to the chlorinated GPA. Correspondingly, the relative expression of the enterococcal vanA resistance gene was shown to be increased by the dechlorinated compared to the chlorinated compound. These results provide insight into the biosynthesis of GPAs and the biological function of GPA chlorination for this medically important class of antibiotic.201830275088
613160.89404-Hydroxy-2-nonenal antimicrobial toxicity is neutralized by an intracellular pathogen. Pathogens encounter numerous antimicrobial responses during infection, including the reactive oxygen species (ROS) burst. ROS-mediated oxidation of host membrane poly-unsaturated fatty acids (PUFAs) generates the toxic alpha-beta carbonyl 4-hydroxy-2-nonenal (4-HNE). Although studied extensively in the context of sterile inflammation, research into 4-HNE's role during infection remains limited. Here, we found that 4-HNE is generated during bacterial infection, that it impacts growth and survival in a range of bacteria, and that the intracellular pathogen Listeria monocytogenes induces many genes in response to 4-HNE exposure. A component of the L. monocytogenes 4-HNE response is the expression of the genes lmo0103 and lmo0613, deemed rha1 and rha2 (reductase of host alkenals), respectively, which code for two NADPH-dependent oxidoreductases that convert 4-HNE to the product 4-hydroxynonanal (4-HNA). Loss of these genes had no impact on L. monocytogenes bacterial burdens during murine or tissue culture infection. However, heterologous expression of rha1/2 in Bacillus subtilis significantly increased bacterial resistance to 4-HNE in vitro and promoted bacterial survival following phagocytosis by murine macrophages in an ROS-dependent manner. Thus, Rha1 and Rha2 are not necessary for 4-HNE resistance in L. monocytogenes but are sufficient to confer resistance to an otherwise sensitive organism in vitro and in host cells. Our work demonstrates that 4-HNE is a previously unappreciated component of ROS-mediated toxicity encountered by bacteria within eukaryotic hosts.202133955352
612170.8940Pathways and roles of wall teichoic acid glycosylation in Staphylococcus aureus. The thick peptidoglycan layers of Gram-positive bacteria are connected to polyanionic glycopolymers called wall teichoic acids (WTA). Pathogens such as Staphylococcus aureus, Listeria monocytogenes, or Enterococcus faecalis produce WTA with diverse, usually strain-specific structure. Extensive studies on S. aureus WTA mutants revealed important functions of WTA in cell division, growth, morphogenesis, resistance to antimicrobials, and interaction with host or phages. While most of the S. aureus WTA-biosynthetic genes have been identified it remained unclear for long how and why S. aureus glycosylates WTA with α- or β-linked N-acetylglucosamine (GlcNAc). Only recently the discovery of two WTA glycosyltransferases, TarM and TarS, yielded fundamental insights into the roles of S. aureus WTA glycosylation. Mutants lacking WTA GlcNAc are resistant towards most of the S. aureus phages and, surprisingly, TarS-mediated WTA β-O-GlcNAc modification is essential for β-lactam resistance in methicillin-resistant S. aureus. Notably, S. aureus WTA GlcNAc residues are major antigens and activate the complement system contributing to opsonophagocytosis. WTA glycosylation with a variety of sugars and corresponding glycosyltransferases were also identified in other Gram-positive bacteria, which paves the way for detailed investigations on the diverse roles of WTA modification with sugar residues.201424365646
8187180.8939Racial disparities in metastatic colorectal cancer outcomes revealed by tumor microbiome and transcriptome analysis with bevacizumab treatment. Background: Metastatic colorectal cancer (mCRC) is a heterogeneous disease, often associated with poor outcomes and resistance to therapies. The racial variations in the molecular and microbiological profiles of mCRC patients, however, remain under-explored. Methods: Using RNA-SEQ data, we extracted and analyzed actively transcribing microbiota within the tumor milieu, ensuring that the identified bacteria were not merely transient inhabitants but engaged in the tumor ecosystem. Also, we independently acquired samples from 12 mCRC patients, specifically, 6 White individuals and 6 of Black or African American descent. These samples underwent 16S rRNA sequencing. Results: Our study revealed notable racial disparities in the molecular signatures and microbiota profiles of mCRC patients. The intersection of these data showcased the potential modulating effects of specific bacteria on gene expression. Particularly, the bacteria Helicobacter cinaedi and Sphingobium herbicidovorans emerged as significant influencers, with strong correlations to the genes SELENBP1 and SNORA38, respectively. Discussion: These findings underscore the intricate interplay between host genomics and actively transcribing tumor microbiota in mCRC's pathogenesis. The identified correlations between specific bacteria and genes highlight potential avenues for targeted therapies and a more personalized therapeutic approach.202338357363
6025190.8938Phenotypic and Genomic Insights into Schleiferilactobacillus harbinensis WU01, a Candidate Probiotic with Broad-Spectrum Antimicrobial Activity Against ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter) Pathogens. The increasing prevalence of multidrug-resistant (MDR) pathogens, particularly ESKAPE bacteria, necessitates alternative antimicrobial strategies. Probiotics, particularly lactic acid bacteria, protect against pathogenic infections. This study aimed to characterize Schleiferilactobacillus harbinensis WU01, isolated from fermented palm sap, and evaluate its probiotic potential and antimicrobial activity. Its probiotic characteristics were assessed based on low-pH and bile tolerance, auto-aggregation, hydrophobicity, and adhesion to Caco-2 cells. Antimicrobial activity against ESKAPE pathogens was evaluated using the agar well diffusion assay. Whole-genome sequencing (WGS) and in silico analysis were performed to identify bacteriocin-related genes, virulence factors, and antibiotic-resistance genes. WU01 exhibited a strong tolerance to gastrointestinal conditions, with high survival rates under acidic and bile-salt environments. S. harbinensis WU01 demonstrated significant auto-aggregation, high hydrophobicity, and strong adhesion to Caco-2 cells. Antimicrobial assays revealed inhibitory activity against MDR ESKAPE pathogens, which correlated with the presence of bacteriocin-related genes, including those homologous to Carnocin_CP52. Molecular dynamics (MDs) simulations confirmed the interaction of Carnocin_CP52 with bacterial membranes, suggesting a mechanism for pathogen disruption. WGS confirmed the absence of virulence and antimicrobial-resistance genes, confirming its safety for probiotic applications. These findings suggest that S. harbinensis WU01 possesses probiotic properties and antimicrobial activity against ESKAPE pathogens. The combined results highlight its potential application in functional foods and therapeutic interventions.202540238333