Critical Reviews in Microbiology最新文献

Acinetobacter baumannii (A. baumannii) has become a major hospital-acquired pathogen, well-known for its rapid development of resistance to multiple antibiotics. The rising incidence of antibiotic-resistant A. baumannii presents a significant global public health challenge. Gaining a deep understanding of the mechanisms behind this resistance is essential for creating effective treatment options. This comprehensive review explores the understanding of various antibiotic resistance mechanisms in A. baumannii. It covers intrinsic resistance, acquired resistance genes, efflux pumps, changes in outer membrane permeability, alterations in drug targets, biofilm formation, and horizontal gene transfer. Additionally, the review investigates the role of mobile genetic elements and the clinical implications of antibiotic resistance in A. baumannii infections. The insights provided may inform the development of new antimicrobial agents and the design of effective infection control strategies to curb the spread of multidrug-resistant (MDR) A. baumannii strains in healthcare environments. Unlike previous reviews, this study offers a more integrative perspective by also addressing the pathogen's environmental resilience, with particular emphasis on its resistance to desiccation and the formation of robust biofilms. It further evaluates both established and emerging therapeutic strategies, thereby expanding the current understanding of A. baumannii persistence and treatment.

The interactions between viruses and protists have been crucially impacting the ecosystem. In recent studies, it has been found that the protists are not only able to consume, ingest or inactivate a variety of viruses, resulting in a reduction of the viral load, but instead, they can treat viruses as the exclusive source of nutrients, exhibiting "Virovory" (virus-only diet). These small protists can act as virosomes (organisms harnessing nutrients from the viruses) and utilize the viruses as the only source of nourishment, implying the protist to multiply and grow. The viral reduction was previously thought to be only because of the action of abiotic factors (temperature, ultraviolet light, chemicals, membrane adsorption, etc.). However, virovory suggests that organic material flow in microbial communities, the impact of viruses on the food web and, the role of protists in regulating viral populations are crucial factors in ecosystem dynamics. In this review, ingestion, digestion, and inactivation of a variety of viruses by protists are discussed. Several questions can be answered by further research on understanding the mechanisms behind the inactivation of viruses, the impact of reduced viral load on other microbial populations, and the large-scale employability of these little protists in removing pathogenic viruses from the environment.

The Flaviviridae family includes many medically relevant members, such as dengue, Zika, West Nile, and hepatitis C viruses, that produce hundreds of millions of infections annually. There is a close relationship between these infections and inflammation triggering as an important part of the host's immune response and of pathogenesis. These inflammatory processes are mediated by the activation of multiprotein complexes known as inflammasomes. Several inflammasomes have been described which differ in their composition and their activating stimuli. The NLRP3 inflammasome is the most studied. Its activation begins by the recognition of pathogen-associated molecular patterns such as viral RNA, potassium efflux, calcium flux, increased reactive oxygen species; and culminates in the maturation and secretion of pro-inflammatory cytokines such as IL-1β and IL-18, and cell death by pyroptosis. This review summarizes the most relevant aspects of NLRP3 inflammasome activation in relevant flavivirus infections from clinical and laboratory studies in biological models. Understanding the activation, mounting, and regulation of the inflammatory response during viral infections is a poorly exploited area of opportunity for the development of efficient and safe treatment strategies, which could include NLRP3 inflammasome inhibition.

The genus Mycobacterium contains over 180 species, and new species are added frequently. Among these are several obligate pathogens, namely Mycobacterium leprae and the species of the Mycobacterium tuberculosis complex; however, the vast majority are environmental bacteria that occupy numerous habitats and are collectively referred to as nontuberculous mycobacteria (NTM). Most NTM are harmless to humans, but the ability of some species to cause infections in people has been increasingly recognized over the past several decades. Mycobacterium avium subs. hominissuis has emerged as one of the most common opportunistic pathogens, usually causing pulmonary infections in susceptible people following environmental exposure. Mycobacterium avium's ability to form biofilms is key to its survival in environments that place it in close proximity to susceptible populations. Their capacity to form biofilms in vivo may also be an important aspect of their pathogenesis and known antibiotic resistance. In this review, we discuss the pathogenesis of this important mycobacterial species, what we know of its ability to form biofilms in vitro and in vivo, and gaps in our knowledge of these processes. We also discuss how we may leverage our understanding of molecules involved in biofilm formation and biofilm matrix composition to develop new therapeutics targeting biofilm formation.

Human fungal infections are increasingly being recognized as a significant global health threat. The burden of fungal diseases is escalating, primarily due to the rising number of at-risk individuals, compounded by the limited availability of antifungal therapies that are both effective and minimally toxic. Phages, viruses that specifically infect and kill bacteria, have long been investigated for their therapeutic potential. However, despite their success in bacteriology, the applications of phages in antifungal therapy are under active research. Particularly, phages could be used to treat fungal infections by engineering them to express fungal antigens on their surfaces, and this would trigger specific immune responses, such as activating Th1 and Th17 responses or inducing the production of neutralizing antibodies. Phages could also be combined with photodynamic inactivation (PDI) or antimicrobials to enhance treatment efficiency. Meanwhile, phages can exert direct antifungal effects by depleting iron, a crucial nutrient for fungal growth. This paper provides a comprehensive review of the phage-based antifungal treatment.

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.