Resistance to last-resort antibiotics in enterococci

Uncovering the effects of copper feed supplementation on the selection of copper-tolerant and antibiotic-resistant Enterococcus in poultry production for sustainable environmental practices

Occurrence of glycopeptide resistance among Enterococcus faecium isolates from conventional and ecological poultry farms.

Extensive use of antibiotics in medicine, veterinary practice and animal husbandry has promoted the development and dissemination of bacterial drug resistance. The number of resistant pathogens causing common infectious diseases increases rapidly and creates worldwide public health problem. Commensal bacteria, including lactic acid bacteria of genera Enterococcus and Lactococcus colonizing gastrointestinal and urogenital tracts of humans and animals may act as vehicles of antibiotic resistance genes similar to those found in pathogens. Lactococci and enterococci are widely used in manufacturing of fermented products and as probiotics, therefore monitoring and control of transmissible antibiotic resistance determinants in industrial strains of these microorganisms is necessary to approve their Qualified Presumption of Safety status. Understanding the nature and molecular mechanisms of antibiotic resistance in enterococci and lactococci is essential, as intrinsic resistant bacteria pose no threat to environment and human health in contrast to bacteria with resistance acquired through horizontal transfer of resistance genes. The review summarizes current knowledge concerning intrinsic and acquired antibiotic resistance in Lactococcus and Enterococcus genera, and discusses role of enterococci and lactococci in distribution of this feature.

The global spread of antibiotic resistance has posed a serious threat to public healthcare and undermined decades of progress made in the fight against bacterial infections. It has been demonstrated that the lack of novel effective antibiotics and rapid spread of antibiotic resistance genes via horizontal transfer in the ecosystem are mainly responsible for this crisis. Notably, plasmid-mediated horizontal transfer of antibiotic resistance genes (ARGs) is recognized as the most dominant dissemination pathway of ARGs in humans, animals and environmental settings. Antibiotic selective pressure has always been regarded as one of the crucial contributors to promoting the dissemination of antibiotic resistance through horizontal gene transfer (HGT). However, the roles of exogenous compounds and particularly non-antibiotic drugs in the spread of ARGs are still underappreciated. In this review, we first summarize the major pathways of HGT in bacteria, including conjugation, transformation, transduction and vesiduction. Subsequently, an overview of these compounds capable of promoting the HGT is presented, which guides to the formulation of more reasonable dosing regimens and drug residue standards in clinical practice. By contrast, these compounds that display an inhibition effect on HGT are also highlighted, which provides a unique strategy to minimize the spread of ARGs. Lastly, we discuss the implementations and challenges in bringing these HGT inhibitors into clinical trials.

Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches.

Various heavy metals are reported to be able to accelerate horizontal transfer of antibiotic resistance genes (ARGs). In real water environmental settings, ubiquitous complexing agents would affect the environmental behaviors of heavy metal ions due to the formation of metal-organic complexes. However, little is known whether the presence of complexing agents would change horizontal gene transfer due to heavy metal exposure. This study aimed to fill this gap by investigating the impacts of a typical complexing agent ethylenediaminetetraacetic acid (EDTA) on the conjugative transfer of plasmid-mediated ARGs induced by a range of heavy metal ions. At the environmentally relevant concentration (0.64 mg L−1) of metal ions, all the tested metal ions (Mg2+, Ca2+, Co2+, Pb2+, Ni2+, Cu2+, and Fe3+) promoted conjugative transfer of ARGs, while an inhibitory effect was observed at a relatively higher concentration (3.20 mg L−1). In contrast, EDTA (0.64 mg L−1) alleviated the effects of metal ions on ARGs conjugation transfer, evidenced by 11 %-66 % reduction in the conjugate transfer frequency. Molecular docking and dynamics simulations disclosed that this is attributed to the stronger binding of metal ions with the lipids in cell membranes. Under metal-EDTA exposure, gene expressions related to oxidative stress response, cell membrane permeability, intercellular contact, energy driving force, mobilization, and channels of plasmid transfer were suppressed compared with the metal ions exposure. This study offers insights into the alleviation mechanisms of complexing agents on ARGs transfer induced by free metal ions.

There is growing concern about the transfer of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in airborne particulate matter. In this study, we investigated the effects of various types of carbonaceous particulate matter (CPM) on the transfer of ARGs in vitro. The results showed that CPM promoted the transfer of ARGs, which was related to the concentration and particle size. Compared with the control group, the transfer frequency was 95.5, 74.7, 65.4, 14.7, and 3.8 times higher in G (graphene), CB (carbon black), NGP (nanographite powder), GP1.6 (graphite powder 1.6 micron), and GP45 (graphite powder 45 micron) groups, respectively. Moreover, the transfer frequency gradually increased with the increase in CPM concentration, while there was a negative relationship between the CPM particle size and conjugative transfer frequency. In addition, the results showed that CPM could promote the transfer of ARGs by increasing ROS, as well as activating the SOS response and expression of conjugative transfer-related genes (trbBp, trfAp, korA, kroB, and trbA). These findings are indicative of the potential risk of CPM for the transfer of ARGs in the environment, enriching our understanding of environmental pollution and further raising awareness of environmental protection.

Nanoscale zero-valent iron alleviated horizontal transfer of antibiotic resistance genes in soil: The important role of extracellular polymeric substances

Photoaged nanoplastics with multienzyme-like activities significantly shape the horizontal transfer of antibiotic resistance genes

Synergistic effect of horizontal transfer of antibiotic resistance genes between bacteria exposed to microplastics and per/polyfluoroalkyl substances: An explanation from theoretical methods.

Presence of bromide and iodide promotes the horizontal transfer of antibiotic resistance genes during chlorination: A preliminary study

Horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs) through plasmid-mediated conjugation poses a major threat to global public health. Biochar, a widely used environmental remediation material, has remarkable impacts on the fate of ARGs. However, although biochar was reported being able to inhibit the HGT of ARGs via conjugation and transformation, little is known about the intracellular process that mediates the inhibition effects. On the other hand, as typical natural organic matter, fulvic acid is a common environmental influencer, and how it interferes with the effect of biochar on the HGT of ARGs is unknown. Therefore, this study investigated the effects on the conjugative transfer of ARGs between Escherichia coli MG1655 and E. coli HB101 carrying plasmid RP4, with biochars pyrolyzed at three temperatures and with the corresponding biochars coating with fulvic acid. Results showed that biochar with higher pyrolyzed temperature had a more substantial inhibitory effect on the conjugative transfer of the RP4 plasmid. The inhibitory effect of biochar was mainly attributed to (i) down-regulation of plasmid transfer gene expression, including the formation of conjugative transfer channel and plasmid replication, due to restrained adenosine triphosphate (ATP) energy supply and (ii) decreased cell membrane permeability. Conversely, the fulvic acid coating diminished this inhibition effect of biochar, mainly by providing more ATP and strengthening intracellular reactive oxygen species (ROS) defense. Our findings shed light on the intracellular process that mediates the effects of biochar on the conjugative transfer of ARGs, which would provide support for using biochar to reduce the spread of ARGs.

Disinfectants are commonly utilized by humans to combat microorganisms. However, residual disinfectants may promote environmental antimicrobial resistance by facilitating horizontal gene transfer (HGT) of antibiotic resistance genes. Bronopol is a routinely used disinfectant that persists in the environment, and previous studies have concentrated on its ecotoxicity rather than its implications on the propagation of resistance genes. This study aimed to establish an in vitro conjugation model to investigate whether bronopol promotes the transfer of antibiotic resistance genes (ARGs) via plasmid conjugation. Using Escherichia coli DH5α and DC8855 as donors harboring RP4-7 and blaNDM-4-positive IncFII(K) plasmids, respectively, and J53 as the recipient strain, we found that sub-inhibitory concentrations of bronopol (2 μg/L and 20 μg/L) significantly increased the conjugative transfer frequency (CTF) of both plasmids. Mechanistic analysis revealed that bronopol enhanced bacterial membrane permeability, as demonstrated by propidium iodide (PI) staining, 1-N-phenylnaphthylamine (NPN) fluorescent probes, transmission electron microscopy (TEM), and upregulation of the outer membrane protein gene ompC. Additionally, bronopol treatment upregulated RP4 plasmid-encoded genes involved in DNA transfer/replication (trfAp) and the global regulator of HGT (kilA/kilB). These findings highlight a previously unrecognized role of bronopol in facilitating the dissemination of antibiotic resistance genes, particularly those of clinical significance.

Plastic particles impact the propagation of antibiotic resistance genes (ARGs) in environmental media, and their perturbation on the horizontal gene transfer (HGT) of ARGs is recognized as a critical influencing mechanism. However, studies concerning the influence and influencing mechanisms of plastic particles on the HGT of ARGs were limited, particularly for the effect of particle sizes and ARG vector-associated mechanisms. This study explored the impact of polystyrene (PS) particles with sizes of 75, 90, 100, 1000, and 10000 nm on the HGT (via transformation) of ARGs mediated by pUC19, pSTV29, and pBR322 plasmids into Escherichia coli cells. PS particles with sizes ≤100 nm impacted the transformation of ARGs, but large particles (1000 and 10000 nm) showed no obvious effects. Effects of PS particles on the transfer of three plasmids were vastly distinct. For pUC19 with high replication capacities, the transfer was monotonously promoted. However, for pSTV29 and pBR322 with low replication capacities, suppressing effects were observed. This was attributed to two competing mechanisms. The enhancing mechanism was that the direct interaction of PS particles with membrane lipids and the indirect effect associated with bacterial oxidative stress response induced pore formation on the cell membrane and increased membrane permeability, thus enhancing plasmid entrance. The inhibiting mechanism was that PS particles interfered with plasmid replication inside E. coli, thus decreasing the bacterial tranformation. This study deepened our understanding of the environmental dissemination of ARGs in plastic contamination.

Antimicrobial resistance (AMR) has become a major global health threat, seriously impairing the efficacy of modern medical anti-infective therapies. With the continuous emergence of multi-drug resistant (MDR) bacteria, the difficulty of clinical infection diagnosis and treatment is increasing, leading to a continuous rise in morbidity, mortality and medical burden. Against this backdrop, the human intestinal microbiota, as a vast microbial ecosystem, plays a key role in regulating host immunity, metabolism and resisting pathogen colonization. The intestinal microbiota is also an important hub for the transmission of antibiotic resistance genes (ARGs). Once the microbiota is imbalanced, that is, when the composition and function of microorganisms are disrupted, it may promote the horizontal transfer of resistance genes, accelerating the colonization and spread of MDR bacteria. This review will systematically elaborate on the role of the intestinal microbiota in the colonization of methicillin-resistant Staphylococcus aureus (MRSA) and how it affects the horizontal transfer of resistance genes, and discuss how to use therapeutic strategies such as probiotics, bacteriophage therapy (BT) and fecal microbiota transplantation (FMT) to curb the spread of resistance, gradually restore microbiota homeostasis, and potentially provide a theoretical basis for the development of targeted microbiota-based personalized treatments to address the increasingly severe problem of resistant bacterial infections.