Critical Reviews in Microbiology最新文献

Endolichenic fungi (ELF) are symbiotic organisms residing in lichens. Since the initial report of its application in natural products and drug discovery, they have emerged as unique valuable sources of compounds with a wide range of structural diversity and biological activities. In this review, we critically examine current strategies to expand ELF metabolite diversity, with emphasis on the One Strain, Many Compounds (OSMAC) approach and metabolomics-guided profiling. We highlight how co-culture systems, epigenetic modifiers, and advanced data acquisition platforms can open new avenues for chemical space exploration. Genomic and transcriptomic studies, though still limited in ELF, reveal untapped biosynthetic potential and point toward integrative omics pipelines. Recent computational and artificial intelligence tools further accelerate genome-metabolome mining, structural elucidation, and prediction of bioactivity. We propose a forward-looking framework that combines OSMAC, integrative omics, and AI to maximize the natural product bioprospecting potential of ELF, while also uncovering their ecological roles within the lichen holobiome.

The metalloid tellurium (Te) is toxic to bacteria; however, the element is also extremely rare. Thus, most bacteria will never encounter Te in their environment. Nonetheless significant research has been performed on bacterial Te resistance because of the medical applications of the element. The so-called "tellurium resistance (Te^R) genes" were first described on plasmids isolated from clinically relevant Enterobacteriaceae. With time, it has become apparent that, given the rarity of Te on the planet, these genes may have functions beyond tellurium resistance. Nonetheless, the description of these genes as "tellurium resistance genes" has persisted. In this review, we first examine the history and discovery of the Te^R genes. We then performed an analysis of 184,000 high-quality, prokaryotic (meta)genomes, which revealed that terZABCDF, telA, and tehAB are relatively common in genome annotations and that they are frequently described as "tellurium resistance genes". We synthesized the literature to describe the functions of these ubiquitous genes beyond tellurium resistance. These genes have functions in diverse cellular processes including phage resistance, antibiotic resistance, virulence, oxidative stress resistance, cell cycle regulation, metal resistance, and metalation of exoenzymes. Considering this analysis, we propose that it is time to appreciate the multifunctional nature of the "tellurium resistance genes".

Foodborne illness is a critical food safety and public health concern, often resulting from contamination events by resident pathogens in food processing environments (FPEs). Listeria monocytogenes, the causative agent of listeriosis, can persist in FPEs over long time periods. Despite rigorous research on the phenotypic and genotypic traits of L. monocytogenes, no clear pattern has arisen to explain why some strains are able to persist. Researchers face definitional and methodological challenges, which influence identification and comparison of persistent and non-persistent strains. Moreover, only weak associations between persistence and gene-level patterns have been detected, necessitating new perspectives. In this review, we synthesize years of research based on whole genome sequencing, highlighting sequence-type and gene-level patterns linked to persistence. As these patterns do not robustly explain persistence, we critically assess how applied definitions and methodological approaches have shaped, and potentially biased, our current understanding. We evaluate existing hypotheses on persistence and suggest future research directions, integrating insights from ecology, evolution, and predictive modeling to disentangle factors and mechanisms that enable L. monocytogenes to persist in food processing environments.

Biofilms are microbial communities that adhere to surfaces and each other, encapsulated in a protective extracellular matrix. These structures enhance resistance to antimicrobials, contributing to 65-80% of human infections. The transition from free-living cells to structured biofilms involves a myriad of molecular and structural adaptations. Raman spectroscopy is an analytical technique that has recently been adapted for biofilm analysis. The ability to operate without interference from water makes Raman spectroscopy a valuable tool for in situ characterization of biofilms, including direct analysis from clinical samples. The technique also offers the advantage of imaging speed and the capacity to generate extensive chemical and molecular data from samples, whilst also being non-destructive. However, Raman spectroscopy is often limited by its low sensitivity, particularly when applied to microbial analysis. This limitation has been addressed with the advent of surface-enhanced Raman spectroscopy and stimulated Raman scattering microscopy. When used in combination with traditional methods, these Raman technologies can be incredibly useful for understanding the mechanisms underlying biofilm development, antimicrobial susceptibility testing, and detection and discrimination of microorganisms. In this critical review, the application of Raman spectroscopy and its derivatives as a tool for biofilm characterization is discussed along with its associated advantages and challenges.

Helicobacter pylori (H. pylori) infection is a common and serious infectious disease that requires eradication as it is the primary cause of gastric adenocarcinoma. However, the growing prevalence of antibiotic resistance, severe side effects, and the inability of current treatments to effectively address biofilm-embedded, intracellular, and dormant H. pylori strains, alongside their long-term gut microbiome disruptions, have rendered standard therapies increasingly ineffective. This predicament underscores the pressing need to explore antibiotic-independent antimicrobial moieties. This pursuit involves a multifaceted approach, encompassing innovative strategies that target critical regulatory points in H. pylori infection. These include the development of urease inhibitors, anti-adhesion therapies, treatments for intracellular H. pylori, strategies for eradicating dormant forms, interventions against biofilm formation, among others. Additionally, various antibiotic-independent antimicrobial moieties that can target multiple bacterial mechanisms and forms are being explored, such as intraluminal photoacoustic therapy, the use of nanoparticles, antimicrobial peptides (AMPs), vaccines, phage therapy, and other cutting-edge treatments. These strategies offer promising prospects for non-antibiotic treatments to overcome this persistent and often debilitating infection.

Nucleos(t)ide analogs constitute a diverse group of compounds derived from nucleosides and nucleotides, playing a crucial role in various biological processes. These analogs exhibit a wide range of applications, including their use as additives, antiviral, and anticancer agents, which makes them valuable in food and medical research. In this review, we will explore the applications of nucleos(t)ide analogs across different fields and discuss the latest advances in engineering and optimization strategies aimed at improving their production efficiency and tailoring their properties for specific purposes. The article focuses on the design of microbial cell factories and their critical role in the production of nucleos(t)ide analogs. By leveraging microbial biosynthesis pathways and employing strategies such as metabolic engineering, researchers are optimizing the synthesis pathways of nucleos(t)ide analogs. This optimization enhances both the yield and diversity of nucleos(t)ide analogs, leading to the creation of novel compounds with enhanced bioactivity and therapeutic potential. Consequently, these efforts are driving significant advancements in drug discovery and biotechnology.

Listeria monocytogenes, a resilient bacterium in diverse food conditions, such as refrigeration, reduced water activity and low pH, poses a significant threat to the food industry and public health. In recent years, it has been documented an increase in the antibiotic resistance of zoonotic pathogens, including L. monocytogenes. This review provides new insight into the molecular mechanisms involved in both intrinsic and acquired antibiotic resistance of L. monocytogenes with an emphasis on the effect of different environmental and food-related factors. It also explores the relationship of these resistance mechanisms with virulence factors. An analysis of literature data (2009-2021) was conducted to investigate statistically and graphically potential associations between specific antibiotic resistance patterns in the pathogen and food categories using an unbiased variance analysis. The results evidenced that food type had an influence on the antibiotic resistance profiles of L. monocytogenes, with meat and vegetables being the food categories exhibiting the most prevalent profiles. The frequent detection of resistance to ampicillin, penicillin, and tetracycline (non-intrinsic resistances) indicates that specific processing conditions along the food chain may induce them. Many questions remain about the impact of food chain factors (e.g. thermal treatments, cold chain, preservatives, etc.) and food type (low pH, reduced water activity, etc.) on the antibiotic resistance patterns of the pathogen, particularly concerning food-related sources, the resistance mechanisms involved (e.g. cross-protection, horizontal gene transfer, etc.), and the evolutionary processes of antibiotic-resistant microbial populations. Metagenomics, in addition to other -omics technologies (metabolomics and transcriptomics), allows a better understanding of the processes involved in the acquisition of resistance.

Antibiotic resistance has expanded as a result of the careless use of antibiotics in the medical field, the food industry, agriculture, and other industries. By means of genetic recombination between commensal and pathogenic bacteria, the microbes obtain antibiotic resistance genes (ARGs). In bacteria, horizontal gene transfer (HGT) is the main mechanism for acquiring ARGs. With the development of high-throughput sequencing, ARG sequence analysis is now feasible and widely available. Preventing the spread of AMR in the environment requires the implementation of ARGs mapping. The metagenomic technique, in particular, has helped in identifying antibiotic resistance within microbial communities. Due to the exponential growth of experimental and clinical data, significant investments in computer capacity, and advancements in algorithmic techniques, the application of machine learning (ML) algorithms to the problem of AMR has attracted increasing attention over the past five years. The review article sheds a light on the application of bioinformatics for the antibiotic resistance monitoring. The most advanced tool currently being employed to catalog the resistome of various habitats are metagenomics and metatranscriptomics. The future lies in the hands of artificial intelligence (AI) and machine learning (ML) methods, to predict and optimize the interaction of antibiotic-resistant compounds with target proteins.

Pseudomonas aeruginosa, able to survive on the surfaces of medical devices, is a life-threatening pathogen that mainly leads to nosocomial infection especially in immunodeficient and cystic fibrosis (CF) patients. The antibiotic resistance in P. aeruginosa has become a world-concerning problem, which results in reduced and ineffective therapy efficacy. Besides intrinsic properties to decrease the intracellular content and activity of antibiotics, P. aeruginosa develops acquired resistance by gene mutation and acquisition, as well as adaptive resistance under specific situations. With in-depth research on drug resistance mechanisms and the development of biotechnology, innovative strategies have emerged and yielded benefits such as screening for new antibiotics based on artificial intelligence technology, utilizing drugs synergistically, optimizing administration, and developing biological therapy. This review summarizes the recent advances in the mechanisms of antibiotic resistance and emerging treatments for combating resistance, aiming to provide a reference for the development of therapy against drug-resistant P. aeruginosa.

Non-tuberculous mycobacteria (NTM) are opportunistic pathogens ubiquitous in the environment. Mycobacteroides abscessus is a relatively new pathogen associated with underlying lung chronic pathologies, accounting for most of the pulmonary infections linked to the rapidly growing mycobacteria group. This includes chronic obstructive pulmonary disease, bronchiectasis, or cystic fibrosis. Patient outcomes from M. abscessus infections are poor due to complicated treatments and other factors. Intrinsic drug resistance plays an important role. The M. abscessus toolbox of resistance is varied leading to complex strategies for treatment. Mechanisms include waxy cell walls, drug export mechanisms, and acquired resistance. Many studies have also shown the impact of extracellular DNA found in the biofilm matrix during early infection and its possible advantage in pathogenicity. In this review, we discuss the current knowledge of early infection focusing on biofilm formation, an environmental strategy, and which treatments prevent its formation improving current antibiotic treatment outcomes in preliminary studies.