Search Results (252)

Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short half-life, toxic side effects, and increasingly severe drug resistance issues. This study aimed to develop a biomimetic nano-drug delivery system to enhance targeting ability, prolong blood circulation, and mitigate resistance of DAP. Methods: DAP-loaded chitosan nanocomposite particles (DAP-CS) were prepared by electrostatic self-assembly. Macrophage membrane vesicles (MM) were prepared by fusion of M1-type macrophage membranes with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). A biomimetic nano-drug delivery system (DAP-CS@MM) was constructed by the coextrusion process of DAP-CS and MM. Key physicochemical parameters, including particle diameter, zeta potential, encapsulation efficiency, and membrane protein retention, were systematically characterized. In vitro immune escape studies and in vivo zebrafish infection models were employed to assess the ability of immune escape and antibacterial performance, respectively. Results: The particle size of DAP-CS@MM was 110.9 ± 13.72 nm, with zeta potential +11.90 ± 1.90 mV, and encapsulation efficiency 70.43 ± 1.29%. DAP-CS@MM retained macrophage membrane proteins, including functional TLR2 receptors. In vitro immune escape assays, DAP-CS@MM demonstrated significantly enhanced immune escape compared with DAP-CS (p < 0.05). In the zebrafish infection model, DAP-CS@MM showed superior antibacterial efficacy over both DAP and DAP-CS (p < 0.05). Conclusions: The DAP-CS@MM biomimetic nano-drug delivery system exhibits excellent immune evasion and antibacterial performance, offering a novel strategy to overcome the clinical limitations of DAP. Full article

Colibacillosis is a poultry disease caused by the pathogenic bacterium Escherichia coli (E. coli). This study is an experimental cross-sectional study using herbal-based test materials from Javanese cardamom and turmeric rhizome as treatments to replace the role of antibiotics that experience drug resistance in several types of bacteria. A total of 32 samples were utilized in this study, separated into two control groups and six treatment groups. The analysis was carried out by an histopathological examination of the lung organs using H&E and ImageJ staining to calculate the area of the slide image. The data results were analyzed statistically with one-way ANOVA method and qualitatively. The outcome of the statistical test showed that the differences were not statistically significant p value = 0.922 [p > 0.05] in all groups, and findings from qualitative histopathology showed morphological differences in the alveoli, parabronchi, and vasculature in the lung organs. Full article

Background: Chryseobacterium indologenes, an environmental bacterium, is increasingly recognized as an emerging nosocomial pathogen, particularly in Asia, and is often characterized by multidrug resistance. Objectives: This study aimed to investigate the genomic features of clinical C. indologenes isolates from Maharaj Nakorn Chiang Mai Hospital, Thailand, to understand their mechanisms of multidrug resistance, virulence factors, and mobile genetic elements (MGEs). Methods: Twelve C. indologenes isolates were identified, and their antibiotic susceptibility profiles were determined. Whole genome sequencing (WGS) was performed using a hybrid approach combining Illumina short-reads and Oxford Nanopore long-reads to generate complete bacterial genomes. The hybrid assembled genomes were subsequently analyzed to detect antimicrobial resistance (AMR) genes, virulence factors, and MGEs. Results: C. indologenes isolates were primarily recovered from urine samples of hospitalized elderly male patients with underlying conditions. These isolates generally exhibited extensive drug resistance, which was subsequently explored and correlated with genomic determinants. With one exception, CMCI13 showed a lower resistance profile (Multidrug resistance, MDR). Genomic analysis revealed isolates with genome sizes of 4.83–5.00 Mb and GC content of 37.15–37.35%. Genomic characterization identified conserved resistance genes (bla_IND-2, bla_CIA-4, adeF, vanT, and qacG) and various virulence factors. Phylogenetic and pangenome analysis showed 11 isolates clustering closely with Chinese strain 3125, while one isolate (CMCI13) formed a distinct branch. Importantly, each isolate, except CMCI13, harbored a large genomic island (approximately 94–100 kb) carrying significant resistance genes (bla_OXA-347, tetX, aadS, and ermF). The absence of this genomic island in CMCI13 correlated with its less resistant phenotype. No plasmids, integrons, or CRISPR-Cas systems were detected in any isolate. Conclusions: This study highlights the alarming emergence of multidrug-resistant C. indologenes in a hospital setting in Thailand. The genomic insights into specific resistance mechanisms, virulence factors, and potential horizontal gene transfer (HGT) events, particularly the association of a large genomic island with the XDR phenotype, underscore the critical need for continuous genomic surveillance to monitor transmission patterns and develop effective treatment strategies for this emerging pathogen. Full article

Vibrio parahaemolyticus is a pathogenic bacterium widely distributed in marine environments, posing significant threats to aquatic organisms and human health. The overuse and misuse of antibiotics has led to the development of multidrug- and pan-resistant V. parahaemolyticus strains. There is an urgent need for novel antibacterial therapies with innovative mechanisms of action. In this work, a genome-scale metabolic network model (GMSN) of V. parahaemolyticus, named VPA2061, was reconstructed to predict the metabolites that can be explored as potential drug targets for eliminating V. parahaemolyticus infections. The model comprises 2061 reactions and 1812 metabolites. Through essential metabolite analysis and pathogen–host association screening with VPA2061, 10 essential metabolites critical for the survival of V. parahaemolyticus were identified, which may serve as key candidates for developing new antimicrobial strategies. Additionally, 39 structural analogs were found for these essential metabolites. The molecular docking analysis of the essential metabolites and structural analogs further investigated the potential value of these metabolites for drug design. The GSMN reconstructed in this work provides a new tool for understanding the pathogenic mechanisms of V. parahaemolyticus. Furthermore, the analysis results regarding the essential metabolites hold profound implications for the development of novel antibacterial therapies for V. parahaemolyticus-related disease. Full article

Background:Enterococcus spp. is the third leading cause of healthcare-associated infections in the American continent, often because of the virulence factors that protect the bacterium against host defenses and facilitate tissue attachment and genetic material exchange. In addition, vancomycin, considered a last-resort treatment, has shown reduced efficacy in Enterococcus spp. strains. However, the relationship between bacterial resistance and virulence factors remains unclear. This study intends to evaluate the prevalence of glycopeptide-resistant genotypes and virulence factors in Enterococcus spp. strains. Methods: Over six months, 159 Enterococcus spp. strains causing nosocomial infections were analyzed. Multiplex PCR was performed to identify species, glycopeptide-resistant genotypes, and 12 virulence factors. Results: The most abundant species identified were Enterococcus faecalis and E. faecium. Vancomycin resistance was observed in 10.7% of the isolates, and the vanA genotype was present in 47% of resistant samples. The main virulence factors detected were acm (54%), which is related to cell adhesion; gel E (66%), a metalloproteinase linked to tissue damage; and the sex pheromones cpd (64%) and ccf (84%), which are involved in horizontal gene transfer. A significant association was found between the prevalence of acm, ccf, and cpd in VRE isolates, indicating the potential dissemination of genes to emerging strains via horizontal gene transfer. In addition, a new E. faecium, which displayed five virulence factors and harbored the vanA sequence type, was identified and registered as ST2700. Conclusions:Enterococcus faecalis and E. faecium are clinically critical due to multidrug resistance and virulence factors like acm, which aids host colonization. Genes ccf and cpd promote resistance spread via horizontal transfer, while the emerging ST2700 strain requires urgent monitoring to curb its virulent, drug-resistant spread. Full article

Secreted bacteriolytic proteases L1 and L5 of the Gram-negative bacterium Lysobacter capsici XL hydrolyze peptide bridges in bacterial peptidoglycans. Such specificity of action determines the prospects of these enzymes for medicine with the view of creating new antimicrobial drugs to combat antibiotic-resistant strains of pathogens. This research concerns the development of successful expression systems for producing active enzymes L1 and L5 in sufficient amounts for comprehensive studies. Based on L. capsici XL strains with deletions in the alpA (enzyme L1) and alpB (enzyme L5) genes and the constructed expression vectors pBBR1-MCS5 P_T5–alpA and pBBR1-MCS5 P_T5–alpB, we obtained expression strains L. capsici P_T5–alpA and L. capsici P_T5–alpB, respectively. The yields of enzymes L1 and L5 in the developed strains increased by 4 and 137 times, respectively, as compared to the wild-type strain. The cultivation of the expression strains was successfully scaled up under non-selective conditions in a 10-L bioreactor. After fermentation, the yields of enzymes L1 and L5 were 35.48 mg/L and 57.11 mg/L, respectively. The developed homologous expression systems of bacteriolytic proteases L1 and L5 have biotechnological value as compared to those obtained by us earlier based on heterologous expression systems, which have lower yields and labor-intensive purification schemes. Full article

Helicobacter pylori is a Gram-negative bacterium that infects almost half of the global population and is linked to gastric conditions like peptic ulcers and gastric cancer, as well as other diseases such as neurological disorders, cardiovascular problems, and iron deficiency anemia. Its survival in the acidic stomach environment is due to virulence factors like urease, flagella, and adhesion proteins (BabA, SabA). Current treatments involve a combination of antibiotics (clarithromycin, metronidazole, amoxicillin, tetracycline) and proton pump inhibitors, but increasing antibiotic resistance, especially to clarithromycin and metronidazole, poses a major challenge. Resistance mechanisms include mutations in drug targets, efflux pump overexpression, and enzymatic degradation of antibiotics. This has prompted exploration of alternative therapies targeting bacterial processes like urease activity, biofilm formation, and metabolic pathways (energy production, amino acid synthesis, iron acquisition). Natural compounds, such as chitosan and plant extracts, show promise in combating H. pylori growth and virulence. Vaccine development is also ongoing, with DNA vaccines showing potential for broad immune responses. However, no vaccine is yet close to widespread clinical use. Full article

The objective of this study was to determine the epidemiological, clinical, and laboratory characteristics of newborns with sepsis in northwestern Mexico, identify the microorganisms causing early- and late-onset sepsis, and assess antimicrobial resistance. Additionally, it sought to associate neonatal characteristics with antimicrobial resistance or mortality. A retrospective study was conducted from August 2021 to April 2023, during which 8382 neonatal clinical records were analyzed to collect epidemiological, clinical, and laboratory characteristics, as well as microorganisms isolated from neonates and their antimicrobial resistance profiles. Of these, 314 neonates with sepsis were included. The incidence of neonatal sepsis was 4% (314/8382), and the mortality was 12.7% (40/314); late-onset sepsis (65.3%) was more frequent than early-onset sepsis (34.7%). Staphylococcus epidermidis was the most frequently isolated bacterium in neonates with sepsis (both early- and late-onset). Gram-positive bacteria, such as Staphylococcus hominis and Enterococcus faecium, were associated with early-onset sepsis, whereas fungi, particularly Candida albicans, were associated with late-onset sepsis. Of the microorganisms, 52.6% were multidrug resistant (MDR), 10.8% were extensively drug resistant (XDR), and 5.5% were pan-drug resistant (PDR). Low birth weight, prematurity, cesarean section, mechanical ventilation, tachycardia, and low hemoglobin and platelet levels, among others, were associated with XDR or MDR microorganisms. In contrast, low birth weight, mechanical ventilation, stroke, unexpected delivery, respiratory distress, tachycardia, convulsive crisis, high procalcitonin, urea, and AST/TGO levels, among others, were associated with mortality. The incidence, types of sepsis, antimicrobial resistance, and associations identified in this study will aid in diagnosing neonatal sepsis earlier and may reduce mortality in our region. Full article

Antimicrobial resistance (AMR) is a global health threat, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the major resistant pathogens. This study reports the isolation of a novel mangrove-derived bacterium, Virgibacillus chiguensis FN33, as identified through genome analysis and the discovery of a new anionic antimicrobial peptide (AMP) exhibiting anti-MRSA activity. The AMP was composed of 23 amino acids, which were elucidated as NH₃-Glu-Gly-Gly-Cys-Gly-Val-Asp-Thr-Trp-Gly-Cys-Leu-Thr-Pro-Cys-His-Cys-Asp-Leu-Phe-Cys-Thr-Thr-COOH. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for MRSA were 8 µg/mL and 16 µg/mL, respectively. FN33 AMP induced cell membrane permeabilization, suggesting a membrane-disrupting mechanism. The AMP remained stable at 30–40 °C but lost activity at higher temperatures and following exposure to proteases, surfactants, and extreme pH. All-atom molecular dynamics simulations showed that the AMP adopts a β-sheet structure upon membrane interaction. These findings suggest that Virgibacillus chiguensis FN33 is a promising source of novel antibacterial agents against MRSA, supporting alternative strategies for drug-resistant infections. Full article

The rapid increase in drug resistance in recent years has become a significant global public health concern. Escherichia coli are ubiquitous bacteria, widely distributed in various environments. This study isolated a bacterial strain (HD-593) from diseased Chinese soft-shelled turtles (Pelodiscus sinensis). The bacterium was identified based on morphology, biochemical tests, and 16S rRNA sequencing, confirming it as E. coli. Drug susceptibility tests revealed that the HD-593 strain was highly resistant to ceftriaxone, enrofloxacin, doxycycline, sulfadiazine, gentamicin, neomycin, florfenicol, carbenicillin, cefradine, erythromycin, penicillin, ampicillin, midecamycin, and streptomycin. Resistance gene analysis confirmed the presence of quinolone resistance genes (oqxA and oqxB), aminoglycoside resistance genes (aac(3)-II and aphA1), a β-lactam resistance gene (blaTEM), and an acylaminol resistance gene (floR) in HD-593. The median lethal dose (LD50) of HD-593 for P. sinensis was 6.53 × 10⁵ CFU/g. Biochemical analysis of serum revealed that HD-593 infection caused a significant reduction in total protein, albumin, and globulin levels, while markedly increasing the levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Histopathological analysis revealed severe intestinal damage characterized by villi detachment and muscle cell necrosis. Additionally, extensive splenocyte necrosis with nuclear marginalization, glomerular swelling, and pronounced hepatic steatosis accompanied by distended sinusoids were observed. This study identified a multidrug-resistant E. coli strain from deceased P. sinensis, suggesting that drug resistance genes may circulate in aquaculture ecosystems, posing potential risks to aquaculture. Full article

Staphylococcus aureus is associated with human infections, being a resistant bacterium involved in serious infections, and its virulence and resistance are linked to oxidative stress. In this study, we review the role of oxidative stress in the pathogenesis of this bacterium and its influence on immune system evasion, antibiotic resistance, and pharmacological targeting. S. aureus infection generates an intense inflammatory response in the host, evidenced by the activation of pro-inflammatory pathways, the exacerbated production of reactive oxygen species (ROS), and cellular oxidative stress. However, the bacterium develops protective mechanisms against damage, including the production of endogenous antioxidants, the formation of biofilms, and the regulation of redox metabolism, favoring pathogenicity and drug resistance. Resistance seems to be related to alterations in redox metabolism, which influences the sensitization of the immune system. Modulation of the redox response has emerged as a promising approach for developing new antibiotics and formulating more effective combination therapies to combat resistant infections. Natural compounds, including flavonoids, terpenes, and quinones, have demonstrated antibacterial properties by inducing oxidative stress in S. aureus. In summary, the involvement of oxidative stress is complex, with an increase in ROS in the infection and a reduction in immune system evasion and resistance, which could be an interesting therapeutic target. Full article

Antibiotic resistance is increasing at an alarming rate worldwide, in large part due to their misuse and improper disposal. Antibiotics administered to treat human and animal diseases, including feed supplements for the treatment or prevention of disease in farm animals, have contributed greatly to the emergence of a multitude of antibiotic-resistant pathogens. Shewanella is one of many bacteria that have developed antibiotic resistance, and in some species, multiple-antibiotic resistance (MAR). Shewanella is a rod-shaped, Gram-negative, oxidase-positive, and H₂S-producing bacterium that is naturally found in the marine environment. In humans, Shewanella spp. can cause skin and soft tissue infections, septicemia, cellulitis, osteomyelitis, and ear and wound infections. Some Shewanella have been shown to be resistant to a variety of antibiotics, including beta-lactams, aminoglycoside, quinolones, third- or fourth-generation cephalosporins, and carbapenems, due to the presence of genes such as the bla_OXA-class D beta-lactamase-encoding gene, bla_AmpC-class-C beta-lactamase-encoding gene, and the qnr gene. Bacteria can acquire and transmit these genes through different horizontal gene-transmission mechanisms such as transformation, transduction, and conjugation. The genes for antibiotic resistance are present on Shewanella chromosomes and plasmids. Apart from this, heavy metals such as arsenic, mercury, cadmium, and chromium can also increase antibiotic resistance in Shewanella due to co-selection processes such as co-resistance, cross resistance, and co-regulation mechanisms. Antibiotics and drugs enter Shewanella spp. through pores or gates in their cell wall and may be ejected from the bacteria by efflux pumps, which are the first line of bacterial defense against antibiotics. Multiple-drug resistant Shewanella can be particularly difficult to control. This review focuses on the phenotypic and genomic characteristics of Shewanella that are involved in the increase in antimicrobial resistance in this bacterium. Full article

Ficus benjamina is a common park tree, with previous reports of some medicinal properties. In this work, we identified and explored phytochemicals from F. benjamina for potential antimicrobial, pro-wound-healing, anti-inflammatory, and effect on cancer cell lines’ proliferation, both experimentally and bioinformatically. Gas chromatography/mass spectrometry (GC/MS) analysis was performed to identify the volatile compounds. The nonvolatile active components of the extract were identified by HPLC and LC-ESI-MS. We found that some drug-resistant microorganisms (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Serratia marcescens, and Salmonella enteritidis) were inhibited by the extract, the 80% fraction, and all the identified flavonoids except quercetin 3-O-rutinoside. Furthermore, the extract and above-mentioned compound also inhibited the growth of biofilm-producing bacterium. The extract and 80% fraction were very potent (p < 0.001) at inducing death of MCF7 and U87 cancer cell cultures and were more effective in that than the chemotherapeutic agent doxorubicin which served as a positive control. Additionally, the extract of F. benjamina, the 80% fraction, and selected phytochemicals had pronounced pro-wound-healing properties. Finally, the extracts, the 80% fraction, caffeic acid, kaempferol 3-O-rutinoside, and kaempferol 3-O-robinobioside significantly inhibited the secretion of pro-inflammatory cytokines, IL-6 and IL-8 (p < 0.001). In conclusion, this comprehensive research revealed convincing and promising indications of significant therapeutic potential of a F. benjamina extract and its active phytochemicals. Full article

Lactiplantibacillus plantarum GUANKE (L. plantarum GUANKE) is a Gram-positive bacterium isolated from the feces of healthy volunteers. Whole-genome sequencing analysis (WGS) revealed that the genome of L. plantarum GUANKE consists of one chromosome and two plasmids, with the chromosome harbors 2955 CDS, 66 tRNAs, and 5 rRNAs. The genome is devoid of virulence factors and Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems. It contains three intact prophage regions and bacteriocin biosynthesis genes (plantaricins K, F, and E), as well as seventeen genomic islands lacking antibiotic resistance or pathogenicity determinants. Functional prediction outcomes identified that the genome of L. plantarum GUANKE is closely related to transcription, carbohydrate transport and metabolism, and amino acid transport and metabolism. Carbohydrate-active enzymes (CAZymes) analysis and GutSMASH analysis revealed that the genome of L. plantarum GUANKE contained 100 carbohydrate-active enzyme genes and two specialized metabolic gene clusters. Safety assessments confirmed that L. plantarum GUANKE neither exhibited β-hemolytic activity nor harbored detectable transferable drug resistance genes. The strain exhibited remarkable acid tolerance and bile salt resistance. Cellular adhesion assays demonstrated moderate binding capacity to Caco-2 intestinal epithelium (4.3 ± 0.007)%. In vitro analyses using lipopolysaccharide (LPS)-stimulated macrophage models demonstrated that L. plantarum GUANKE significantly suppressed the secretion of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), exhibiting dose-dependent anti-inflammatory activity. In vivo experiments showed that L. plantarum GUANKE was involved in the regulation of the apical junction pathway and interferon pathway in colon tissue of normal mice. Full article

Acne vulgaris is one of the most common skin diseases, and its development is closely linked to the overgrowth of the bacterium Cutibacterium acnes. More than half of the strains of this bacterium are resistant to antibiotics, which has prompted scientists to look for alternatives, such as antibacterial peptides, that can replace traditional drugs. Due to its antioxidant properties, ascorbic acid may be a promising ally in the treatment of acne. The aim of our study was to evaluate the effect of peptide (KWK)₂-KWWW-NH₂(P5) in the presence of ascorbic acid (AA) and its derivative (3-O-ethyl-L-ascorbic acid, EAA) on the stability and organization of phosphatidylinositol monolayers (PI) at temperatures of 25–35 °C. This study showed that the monolayers were in the expanded liquid state (35.28–49.95 mN/m) or in the transition between the expanded liquid and condensed phases (51.50–57.49 mN/m). Compression and decompression isotherms indicated the highest flexibility of the PI + P5 system, where the compression reversibility coefficient of isotherm values ranged from 80.59% to 97.77% and increased for each loop with increasing temperature. At 35 °C, the surface pressure of the monolayer in the PI + P5, PI + P5 + AA and PI + P5 + EAA systems changed less with time. Full article