Antimicrobial resistance (AMR) poses a serious global health concern, resulting in a significant number of deaths annually due to infections that are resistant to treatment. Amidst this crisis, antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics (ATBs). These cationic peptides, naturally produced by all kingdoms of life, play a crucial role in the innate immune system of multicellular organisms and in bacterial interspecies competition by exhibiting broad-spectrum activity against bacteria, fungi, viruses, and parasites. AMPs target bacterial pathogens through multiple mechanisms, most importantly by disrupting their membranes, leading to cell lysis. However, bacterial resistance to host AMPs has emerged due to a slow co-evolutionary process between microorganisms and their hosts. Alarmingly, the development of resistance to last-resort AMPs in the treatment of MDR infections, such as colistin, is attributed to the misuse of this peptide and the high rate of horizontal genetic transfer of the corresponding resistance genes. AMP-resistant bacteria employ diverse mechanisms, including but not limited to proteolytic degradation, extracellular trapping and inactivation, active efflux, as well as complex modifications in bacterial cell wall and membrane structures. This review comprehensively examines all constitutive and inducible molecular resistance mechanisms to AMPs supported by experimental evidence described to date in bacterial pathogens. We also explore the specificity of these mechanisms toward structurally diverse AMPs to broaden and enhance their potential in developing and applying them as therapeutics for MDR bacteria. Additionally, we provide insights into the significance of AMP resistance within the context of host-pathogen interactions.

The good antimicrobial properties of silver make it widely used in food, medicine, and environmental applications. However, the release and accumulation of silver-based antimicrobial agents in the environment is increasing with the extensive use of silver-based antimicrobials, and the prevalence of silver-resistant bacteria is increasing. To prevent the emergence of superbugs, it is necessary to exercise rational and strict control over drug use. The mechanism of bacterial resistance to silver has not been fully elucidated, and this article provides a review of the progress of research on the mechanism of bacterial resistance to silver. The results indicate that bacterial resistance to silver can occur through inducing silver particles aggregation and Ag+ reduction, inhibiting silver contact with and entry into cells, efflux of silver particles and Ag+ in cells, and activation of damage repair mechanisms. We propose that the bacterial mechanism of silver resistance involves a combination of interrelated systems. Finally, we discuss how this information can be used to develop the next generation of silver-based antimicrobials and antimicrobial therapies. And some antimicrobial strategies are proposed such as the \"Trojan Horse\" - camouflage, using efflux pump inhibitors to reduce silver efflux, working with \"minesweeper\", immobilization of silver particles.

Advancement in the area of anti-tubercular drug development has been full-fledged, yet, a very less number of drug molecules have reached phase II clinical trials, and therefore \"End-TB\" is still a global challenge. Inhibitors to specific metabolic pathways of Mycobacterium tuberculosis (Mtb) gain importance in strategizing anti-tuberculosis drug discovery. The lead compounds that target DNA replication, protein synthesis, cell wall biosynthesis, bacterial virulence and energy metabolism are emerging as potential chemotherapeutic options against Mtb growth and survival within the host. In recent times, the in silico approaches have become most promising tools in the identification of suitable inhibitors for specific protein targets of Mtb. An update in the fundamental understanding of these inhibitors and the mechanism of interaction may bring hope to future perspectives in novel drug development and delivery approaches. This review provides a collective impression of the small molecules with potential antimycobacterial activities and their target pathways in Mtb such as cell wall biosynthesis, DNA replication, transcription and translation, efflux pumps, antivirulence pathways and general metabolism. The mechanism of interaction of specific inhibitor with their respective protein targets has been discussed. The comprehensive knowledge of such an impactful area of research would essentially reflect in the discovery of novel drug molecules and effective delivery approaches. This narrative review encompasses the knowledge of emerging targets and promising chemical inhibitors that could potentially translate in to the anti-TB-drug discovery.

In MDR-TB, mycobacterium is resistant to battlefront drugs like rifampicin and isoniazid. Now it\'s an urgent global challenge for treatment & diagnosis because more than 50% of drugs are resistant. Till today\'s information, 5 reasons are liable for MDR: (1) Errors of physicians/patients in therapy management, (2) Complexity and poor vascularization of granulomatous lesions, which obstruct drug distribution to some sites, leading to resistance development, (3) Intrinsic drug resistance of tubercle bacilli, (4) Formation of non-replicating, drug-tolerant bacilli inside the granulomas, (5) Development of mutations in Mtb genes, which are the foremost important molecular mechanisms of resistance. the most contribution of this work is a brief & clear explanation of things chargeable for resistant development, and recent diagnostic & treatment methods for MDR-TB. This study shall help researchers & scientists to develop replacement rapid diagnostic tools, drugs, and treatment protocols.

Managing antibiotic resistance is a significant challenge in modern pharmacotherapy. While molecular analyses have identified efflux pump expression as an essential mechanism underlying multidrug resistance, the targeted drug development has occurred slower. Thus, considering the verification that terpenes can enhance the activity of antibiotics against resistant bacteria, the present study gathered evidence pointing to these natural compounds as bacterial efflux pump inhibitors. A systematic search for manuscripts published between January 2007 and January 2022 was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and the following search terms: \"Terpene\"; AND \"Efflux pump\"; and \"Bacteria.\" From a total of 101 articles found in the initial search, 41 were included in this review. Seventy-five different terpenes, 63 bacterial strains, and 22 different efflux pumps were reported, with carvacrol, Staphylococcus aureus SA-1199B, and NorA appearing most frequently mentioned terpene, bacterial strain, and efflux pump (EP), respectively. The Chi-Squared analysis indicated that terpenes are significantly effective EP inhibitors in Gram-positive and Gram-negative strains, with the inhibitory frequency significantly higher in Gram-positive strains. The results of the present review suggest that terpenes are significant efflux pump inhibitors and, as such, can be used in drug development targeting the combat of antibacterial resistance.

Antimicrobial resistance to treatments for Clostridioides difficile infection (CDI) poses a significant threat to global health. C. difficile is widely thought to be susceptible to oral vancomycin, which is increasingly the mainstay of CDI treatment. However, clinical labs do not conduct C. difficile susceptibility testing, presenting a challenge to detecting the emergence and impact of resistance. In this systematic review, we describe gene determinants and associated clinical and laboratory mechanisms of vancomycin resistance in C. difficile, including drug-binding site alterations, efflux pumps, RNA polymerase mutations, and biofilm formation. Additional research is needed to further characterize these mechanisms and understand their clinical impact.

The significant increase in the number of antibiotic-resistant microorganisms observed in recent years is a public health problem worldwide. One of the molecular mechanisms for the formation of antimicrobial resistance in bacteria is the presence of efflux pumps. The review presents an analysis of experimental studies related to the study of efflux pumps in clinical strains of Pseudomonas aeruginosa, one of the representatives of hospital pathogens of the ESKAPE group. This review is intended for specialists developing new types of drugs against antibiotic-resistant strains, as well as researchers studying the mechanisms of bacterial resistance to antibiotics, heavy metals, biocides and other antimicrobial factors.

Heavy metal contamination poses a serious environmental hazard, globally necessitating intricate attention. Heavy metals can cause deleterious health hazards to humans and other living organisms even at low concentrations. Environmental biotechnologists and eco-toxicologists have rigorously assessed a plethora of bioremediation mechanisms that can hamper the toxic outcomes and the molecular basis for rejuvenating the hazardous impacts, optimistically. Environmental impact assessment and restoration of native and positive scenario has compelled biological management in ensuring safety replenishment in polluted realms often hindered by heavy metal toxicity. Copious treatment modalities have been corroborated to mitigate the detrimental effects to remove heavy metals from polluted sites. In particular, Biological-based treatment methods are of great attention in the metal removal sector due to their high efficiency at low metal concentrations, ecofriendly nature, and cost-effectiveness. Due to rapid multiplication and growth rates, bacteria having metal resistance are advocated for metal removal applications. Evolutionary implications of coping with heavy metals toxicity have redressed bacterial adaptive/resistance strategies related to physiological and cross-protective mechanisms. Ample reviews have been reported for the bacterial adaptive strategies to cope with heavy metal toxicity. Nevertheless, a holistic review summarizing the redox reactions that address the cross-reactivity mechanisms between metallothionein synthesis, extracellular polysaccharides production, siderophore production, and efflux systems of metal resistant bacteria are scarce. Molecular dissection of how bacteria adapt themselves to metal toxicity can augment novel and innovative technologies for efficient detoxification, removal, and combat the restorative difficulties for stress alleviations. The present comprehensive compilation addresses the identification of newer methodologies, summarizing the prevailing strategies of adaptive/resistance mechanisms in bacterial bioremediation. Further pitfalls and respective future directions are enumerated in invigorating effective bioremediation technologies including overexpression studies and delivery systems. The analysis will aid in abridging the gap for limitations in heavy metal removal strategies and necessary cross-talk in elucidating the complex cascade of events in better bioremediation protocols.

Quinolones are broad-spectrum antibiotics, which are used for the treatment of different infectious diseases associated with Enterobacteriaceae. During recent decades, the wide use as well as overuse of quinolones against diverse infections has led to the emergence of quinolone-resistant bacterial strains. Herein, we present the development of quinolone antibiotics, their function and also the different quinolone resistance mechanisms in Enterobacteriaceae by reviewing recent literature.
All data were extracted from Google Scholar search engine and PubMed site, using keywords; quinolone resistance, Enterobacteriaceae, plasmid-mediated quinolone resistance, etc.
The acquisition of resistance to quinolones is a complex and multifactorial process. The main resistance mechanisms consist of one or a combination of target-site gene mutations altering the drug-binding affinity of target enzymes. Other mechanisms of quinolone resistance are overexpression of AcrAB-tolC multidrug-resistant efflux pumps and downexpression of porins as well as plasmid-encoded resistance proteins including Qnr protection proteins, aminoglycoside acetyltransferase (AAC(6\')-Ib-cr) and plasmid-encoded active efflux pumps such as OqxAB and QepA. The elucidation of resistance mechanisms will help researchers to explore new drugs against the resistant strains.

BACKGROUND: Efflux of antibiotics is an effective resistance mechanism among antibiotic-resistant Staphylococcus aureus. This systematic review aims to evaluate the frequency and expression of efflux pump genes in S.aureus around the world.
METHODS: A comprehensive literature search of several databases (Medline Pub Med, ISI, Scopus, Google Scholar, ISC, Science direct and Persian Journals Online, and citation lists) was performed. We considered published studies from 2001 to 2018. Articles reporting the prevalence and expression of efflux pump genes were selected.
RESULTS: Among 183 articles, 36 studies were selected. Of the 36, 23 articles were conducted in Asia.6 in Europe, 5 in America and 2 in African countries. In most of these studies norA, norB, qacA/B genes were commonly evaluated by molecular methods. The presence of efflux pump genes such as norA, norB, norC, mepA, mdeA, qacA/B was detected by PCR in 21 studies and over-expression of genes were reported in 13 studies. The most frequently reported genes in Asia were norA (75%), norB (60%), mepA (35%), mdeA (33%) and qacA/B (20.8%). In European studies, the prevalence of norB was mostly reported among S.aureus isolates and norA and qacA/B were commonly found in similar studies in America. The investigation of gene expression patterns showed that norA was most frequent single-pattern in Asia and America, norB or mdeA in Europe.
CONCLUSIONS: According to this study MDR efflux pumps not only cause high-level resistance but also it considerably associated with over-expression of these genes. Due to the selective pressure on MRSA isolate, the enormous diversity of plasmid-encoded genes had been recorded in different regions, owing to the various numbers and types of isolates in each study or types of disinfectants for general use.