Folia microbiologica最新文献

Structured communities of microbial cells within an extracellular polymeric matrix, called biofilms are a significant cause of the persistence and severity of chronic infection. These biofilm-mediated infections pose significant complications in the treatment plans since they are more resistant to conventional antimicrobial drugs and they are also resistant to the host immune system. Hence, new approaches should be warranted over the traditional therapies to counter such infections. The use of biosurfactants is one of the promising strategies, as these amphiphilic molecules that are produced by microorganisms are present naturally and have strong antibiofilm capabilities. Biosurfactants, including rhamnolipids, sophorolipids, and lipopeptides, work in a range of ways, including interfering with the integrity of biofilms, modulation of microbial adhesion, and quorum sensing. This review discusses the biofilm characteristics and the step of biofilm development along with the detailed analyses of the major biosurfactants and their mechanisms of action as an alternative to the conventional therapy. Moreover, we have pointed out the most recent case studies on biosurfactants with their antibiofilm activities as well as biosurfactant-coated surfaces in biofilm prevention on medical devices to provide the new opportunities in managing biofilm-related infections. Overall, this review brings the better understanding about different biosurfactants to integrate it into clinical treatments.

Strain CCM 2573 is a Gram-positive bacterium that has been intensively studied in the past due to its distinct chemotaxonomic properties, but its reliable taxonomic classification has not been satisfactorily clarified. Whole-genome sequencing and comparative genomic analyses performed in this study revealed that the strain belongs to the Macrococcus caseolyticus phylogenetic clade. Genome-to-genome comparisons confirmed the closest relationship to the type strains of M. caseolyticus subsp. hominis CCM 7927^T and M. caseolyticus subsp. caseolyticus DSM 20597^T. However, the strain harbored unique genomic elements distinguishing it from its nearest phylogenetic neighbors. Its accessory genome contains dozens of insertion sequences, a 92-kbp composite transposon with unique palindromic repeat loci associated with a CRISPR-Cas adaptive immune system, a pseudo-staphylococcal chromosome cassette, and several additional genomic islets. Unlike other macrococci, strain CCM 2573 exhibits a specific peptidoglycan composition (L-Lys-Gly₂-Ser₂-Gly) and shows a higher phylogenetic divergence of aminoacyltransferases (FemABX) involved in interpeptide bridge synthesis. In addition, it reveals distinct biochemical characteristics from both subspecies of M. caseolyticus, particularly in its ability to produce acid from galactose, cellobiose, melezitose, and turanose, as well as in its susceptibility to novobiocin. The MALDI-TOF mass spectra enable differentiation of the strain from other type strains of the genus Macrococcus. The results of polyphasic taxonomy obtained in this study showed that strain CCM 2573 belongs to the species M. caseolyticus, but it is distinct from both validly named M. caseolyticus subspecies. We propose to assign the analyzed strain as a new subspecies, Macrococcus caseolyticus subsp. lactis subsp. nov. The type strain is CCM 2573^T (= DSM 20227^T).

Endophytic bacteria associated with medicinal plants are a vital component of the plant microbiome and represent a valuable biological resource. This study investigates the diversity and biological activities of endophytic bacteria isolated from the flowers of Vernonia anthelmintica, a medicinal plant native to China. The research focuses on evaluating the cytotoxic, antimicrobial, antioxidant, and antidiabetic properties of natural products derived from these bacteria, as well as their effects on melanin synthesis and tyrosinase activity in B16 cells. A total of 32 bacterial strains were isolated and cultured, of which eight crude extracts exhibiting antimicrobial activity were selected for further analysis. These isolates. belong to four genera: Bacillus, Streptococcus, Priestia and Paenibacillus. Among them, Priestia megaterium XJB-41 demonstrated the most substantial pharmacological potential, warranting further investigation to optimize its culture conditions for enhanced bioactive compound production. The optimal growth conditions for P. megaterium XJB-41 were determined to be LB and Nutrient Broth (NB) media, with peptone as the carbon source and yeast extract as the nitrogen source, under 24 h of incubation. These conditions significantly enhanced both bacterial growth and metabolite yield. Moreover, two secondary metabolites: cyclo(D-leu-L-pro) [1] and 2-benzoxazolone [2] were isolated for the first time from the ethyl acetate fraction of P. megaterium XJB-41. This strain shows promise for further investigation as a potential source of therapeutic agents.

Mycobacterium leprae (M. leprae) is the bacterium that causes leprosy. It is a public health problem in many regions, especially in developing countries. The situation is getting worse and worse as drug resistance spreads. InhA is one of the most important proteins for M. leprae's survival. It helps make mycolic acid, an important part of the bacterial cell envelope; hence, InhA is a good target for developing new anti-leprosy drugs. In this study, we focused on identifying natural plant-derived compounds (phytochemicals) capable of inhibiting InhA function using sophisticated computer-based techniques, including molecular docking, simulations, DFT calculations, and machine learning. After structure-based virtual screening, docking scores helped us narrow down the list to Hinokiflavone, 3,29-Dibenzoyl Rarounitriol, and 4'-O-Methylochnaflavone. Molecular dynamics simulations (500 ns) showed that Hinokiflavone and 4'-O-Methylochnaflavone had stable binding and only small changes, which confirmed that the protein-ligand interactions were strong. Principal Component Analysis (PCA) and Free Energy Landscape (FEL) analyses showed that the InhA-ligand complexes were stable in shape and exhibited clear low-energy states. Frontier Molecular Orbital (FMO) analysis showed that the reactivity and electronic profiles were good, especially for Hinokiflavone, which had a small HOMO-LUMO gap. Furthermore, a machine-learning-based QSAR model was used to predict the biological activity values (pIC₅₀) of these compounds post-simulation. The best KNN model showed that the pIC₅₀ values of these compounds were greater than 7.0, exceeding the activity threshold of pIC₅₀ ≥ 6.0. This means they are active inhibitors. These results underscore the potential of these phytochemicals as InhA inhibitors for the management of M. leprae infections and offer a robust in silico prediction for subsequent experimental validation.

Antimicrobial Resistance (AMR) remains a global health threat, with efflux pump-based mechanisms being a significant contributor to bacterial drug resistance, highlighting the importance of exploring alternative strategies such as plant-based phytochemicals. Pseudomonas aeruginosa is a pathogen that heavily depends on its Resistance-Nodulation-Division (RND) efflux systems, like MexAB-OprM, as its resistance pathway against antibiotics. By inhibiting these efflux pumps, the pathogen can potentially be susceptible to the same antibiotics it was resistant to. Phytochemicals derived from medicinal plants offer a large scale of bioactive compounds with potential efflux inhibitory properties. However, the inhibitory effects and activity of bioactive compounds from Brassica nigra and Foeniculum vulgare remain largely unexplored, especially with P. aeruginosa. In this study, the crude extracts from mustard and fennel were evaluated for their ability to affect the efflux resistance in P. aeruginosa PA7 (MTCC 1688). Mustard extract demonstrated a stronger inhibitory effect and increased antibiotic susceptibility compared to Fennel extract, which was supported by intracellular accumulation and bacterial growth behaviour. GC-MS profiling helped identify key components of the extract, and molecular docking revealed that mustard-based compounds showed a higher affinity towards the MexB protein. Molecular dynamics simulations further confirmed the stability of compounds from mustard and MexB interactions as potential ligands. Overall, the findings suggest that the mustard phytochemicals may be a promising natural efflux pump inhibitor capable of increasing the potency of antibiotic activity against P.aeruginosa, increasing their relevance in combating AMR.

Autophagy is an essential intracellular degradation and recycling system for macromolecules and organelles, crucial for cell survival under nutrient stress conditions. In fungi, the genes involved in vesicle assembly during autophagy have been extensively characterized. However, in the pathogen Cryptococcus neoformans, the autophagy pathway remains less understood, particularly regarding its potential connections with virulence and pathogenicity. Our previous work identified Gpp2 as a key player in the biosynthesis of the sulfur-containing amino acid methionine. Through transcriptomic analysis, we observed that through transcriptomic analysis, we observed that deletion of GPP2 in C. neoformans leads to the repression of several core autophagy genes (ATG1, ATG2, ATG4, ATG15, VPS15, and VPS30), likely as an indirect consequence of altered methionine metabolism, while upregulating PEP4 expression. Since methionine is known to repress autophagy in Saccharomyces cerevisiae, we hypothesized that this amino acid might similarly regulate autophagy in C. neoformans. Our experiments demonstrated that both endogenous and exogenous methionine inhibit the expression of autophagy-related genes not only in the wild-type H99 strain but also in gpp2Δ and gpr4Δ mutant strains. Intriguingly, we found that GPR4 deletion creates a mutant unable to sense exogenous methionine, consequently releasing the repression of autophagy genes. Furthermore, microscopic analyses revealed that methionine supplementation substantially reduces autophagosome formation compared to methionine-deprived conditions. These results lead us to conclude that methionine biosynthesis regulation in gpp2Δ strains affects autophagy similarly to S. cerevisiae; GPR4 encodes a functional methionine receptor in C. neoformans; and methionine availability directly impacts autophagic flux, where the methionine receptor Gpr4 links extracellular amino acid availability to the intracellular control of autophagy likely via the Cys3/Gpp2 regulatory axis. This work provides crucial insights into the metabolic regulation of autophagy in pathogenic fungi and opens new avenues for understanding fungal pathogenesis mechanisms.

Methicillin-resistant Staphylococcus aureus (MRSA) is indeed a significant public health issue, affecting millions of people worldwide which can range from mild skin infections to life-threatening conditions like bloodstream infections and pneumonia. The aim of the current study is to decipher the possible mechanism of some selected natural compounds against MRSA. The natural compounds were selected based on our earlier systematic literature review. The selected compounds were screened against various targets of MRSA using molecular docking techniques. The stability of selected compounds was checked using molecular dynamics. Further, Absorption, Distribution, Metabolism and Excretion (ADME) was predicted using QikProp module. All the computational studies were conducted using the Schrodinger Maestro version 13.5.128. In-vitro assays were conducted to check the anti-bacterial effects of selected natural compounds against MRSA. Among 60 selected natural compounds, theasinensin A, xanthohumol, luteolin, oxyresveratrol, liquiritigenin and baicalin has shown the energetically favoured binding conformation in the active site of targets. Further, molecular dynamics results have shown the stable conformation of xanthohumol and theasinensin A in the active site of targets. Further, the pharmacokinetic profile of xanthohumol was found to be better among other natural compounds. The minimum inhibitory concentration (MIC) of xanthohumol was found to be 3.12 µg/mL as indicated by disk diffusion and micro broth dilution assays. Xanthohumol can be promising anti-bacterial agent against MRSA through multi modal mechanism. However, further detailed experimental studies are required to confirm its possible antibacterial mechanisms.