Bacterial antibiotic resistance : combinations of biochemical and genetic mechanisms

The use of antibiotics, often excessive, promotes the development of bacterial resistance, frequently resulting in therapeutic failure. Bacterial resistance can be intrinsic or acquired. Intrinsic resistance is species or genus specific and define the spectrum of activity of the antibiotic. Acquired resistance is only present in certain strains of the species or genus. It is due either to a mutation in a gene located in the host chromosome or in a plasmid, or to the acquisition of genetic information by a bacterium, mainly by conjugation or transformation.L'utilisation, souvent abusive, des antibiotiques favorise l'évolution des bactéries vers la résistance entraînant fréquemment des échecs thérapeutiques. La résistance bactérienne peut être intrinsèque ou acquise. La résistance intrinsèque est spécifique d'espèce ou de genre et définit le spectre d'activité de l'antibiotique. La résistance acquise est présente seulement dans certaines souches de l'espèce ou du genre. Elle est le résultat de mutations dans un gène localisé dans le chromosome de la bactérie ou dans un plasmide ou celui de l'acquisition d'informations génétiques, principalement par conjugaison ou transformation

Competition between VanU G Repressor and VanR G Activator Leads to Rheostatic Control of vanG Vancomycin Resistance Operon Expression

International audienceEnterococcus faecalis BM4518 is resistant to vancomycin by synthesis of peptidoglycan precursors ending in D-alanyl-D-serine. In the chromosomal vanG locus, transcription of the resistance genes from the P-YG resistance promoter is inducible and, upstream from these genes, there is an unusual three-component regulatory system encoded by the vanURS(G) operon from the P-UG regulatory promoter. In contrast to the other van operons in enterococci, the vanG operon possesses the additional vanU(G) gene which encodes a transcriptional regulator whose role remains unknown. We show by DNase I footprinting, RT-qPCR, and reporter proteins activities that VanU(G), but not VanR(G), binds to P-UG and negatively autoregulates the vanURSG operon and that it also represses PYG where it overlaps with VanR(G) for binding. In clinical isolate BM4518, the transcription level of the resistance genes was dependent on vancomycin concentration whereas, in a Delta vanUG mutant, resistance was expressed at a maximum level even at low concentrations of the inducer. The binding competition between VanU(G) and VanR(G) on the P-YG resistance promoter allowed rheostatic activation of the resistance operon depending likely on the level of VanR(G) phosphorylation by the VanS(G) sensor. In addition, there was cross-talk between VanS(G) and VanR'(G), a VanR(G) homolog, encoded elsewhere in the chromosome indicating a sophisticated and subtle regulation of vancomycin resistance expression by a complex two-component system

Evaluation of the BBL CrystalTM MRSA ID System for Rapid Detection of Methicillin Resistance in Staphylococcus aureus

Twenty-four clinical isolates of Staphylococcus aureus collected from various geographic areas and four reference strains were studied by (i) agar diffusion with disks impregnated with 5 μg oxacillin and reading after incubation at 30°C for 24 hours, (ii) Southern hybridization with a probe specific for the mecA gene, and (iii) the BBL CrystalTM MRSA ID system. There was perfect correlation between the three methods: the BBL CrystalTM MRSA ID system detected methicillin resistance in the fifteen strains hybridizing with the mecA probe and classified as resistant by the oxacillin disk diffusion test; the thirteen remaining strains were susceptible by agar diffusion and by the BBL test and did not hybridize with the mecA probe. The BBL CrystalTM MRSA ID System, therefore, appears to be an accurate method for rapid detection of Staphylococcus aureus exhibiting homogeneous resistance to methicillin

Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in Acinetobacter baumannii

International audienceABSTRACT : Acinetobacter baumannii is a nosocomial pathogen of increasing importance due to its multiple resistance to antibiotics and ability to survive in the hospital environment linked to its capacity to form biofilms. To fully characterize the contribution of AdeABC, AdeFGH, and AdeIJK resistance-nodulation-cell division (RND)-type efflux systems to acquired and intrinsic resistance, we constructed, from an entirely sequenced susceptible A. baumannii strain, a set of isogenic mutants overexpressing each system following introduction of a point mutation in their cognate regulator or a deletion for the pump by allelic replacement. Pairwise comparison of every derivative with the parental strain indicated that AdeABC and AdeFGH are tightly regulated and contribute to acquisition of antibiotic resistance when overproduced. AdeABC had a broad substrate range, including β-lactams, fluoroquinolones, tetracyclines-tigecycline, macrolides-lincosamides, and chloramphenicol, and conferred clinical resistance to aminoglycosides. Importantly, when combined with enzymatic resistance to carbapenems and aminoglycosides, this pump contributed in a synergistic fashion to the level of resistance of the host. In contrast, AdeIJK was expressed constitutively and was responsible for intrinsic resistance to the same major drug classes as AdeABC as well as antifolates and fusidic acid. Surprisingly, overproduction of AdeABC and AdeIJK altered bacterial membrane composition, resulting in decreased biofilm formation but not motility. Natural transformation and plasmid transfer were diminished in recipients overproducing AdeABC. It thus appears that alteration in the expression of efflux systems leads to multiple changes in the relationship between the host and its environment, in addition to antibiotic resistance.IMPORTANCE: Increased expression of chromosomal genes for RND-type efflux systems plays a major role in bacterial multidrug resistance. Acinetobacter baumannii has recently emerged as an important human pathogen responsible for epidemics of hospital-acquired infections. Besides its remarkable ability to horizontally acquire resistance determinants, it has a broad intrinsic resistance due to low membrane permeability, endogenous resistance genes, and antibiotic efflux. The study of isogenic mutants from a susceptible A. baumannii clinical isolate overproducing or deleted for each of the three major RND-type pumps demonstrated their major contribution to intrinsic resistance and to the synergism between overproduction of an efflux system and acquisition of a resistance gene. We have also shown that modulation of expression of the structural genes for the efflux systems results in numerous alterations in membrane-associated cellular functions, in particular, in a decrease in biofilm formation and resistance gene acquisition

The Battle against Emerging Antibiotic Resistance: Should Fluoroquinolones Be Used to Treat Children?

Inappropriate use of antibiotic drugs in humans and animals has led to widespread resistance among microbial pathogens. Resistance is the phenotypic expression corresponding to genetic changes caused by either mutation or acquisition of new genetic information. In some cases, multidrug resistance occurs. Streptococcus pneumoniae is one of the most important respiratory pathogens, playing a major role in both upper and lower respiratory tract infections. Pneumococcal resistance to antimicrobials may be acquired by means of horizontal transfer followed by homologous recombination of genetic material from the normal flora of the human oral cavity or by means of mutation. Resistance to penicillins and macrolides has been increasing for some time, but, recently, fluoroquinolone resistance has become an issue as well. We are concerned that, if fluoroquinolones are approved for use in children, their widespread use will result in rapid emergence of pneumococcal resistance, because children are more often colonized in the nasopharynx with high-density populations of pneumococci than are adult

Reducing antibiotic prescribing and addressing the global problem of antibiotic resistance by targeted hygiene in the home and everyday life settings: A position paper

Antimicrobial resistance (AMR) continues to threaten global health. Although global and national AMR action plans are in place, infection prevention and control is primarily discussed in the context of health care facilities with home and everyday life settings barely addressed. As seen with the recent global SARS-CoV-2 pandemic, everyday hygiene measures can play an important role in containing the threat from infectious microorganisms. This position paper has been developed following a meeting of global experts in London, 2019. It presents evidence that home and community settings are important for infection transmission and also the acquisition and spread of AMR. It also demonstrates that the targeted hygiene approach offers a framework for maximizing protection against colonization and infections, thereby reducing antibiotic prescribing and minimizing selection pressure for the development of antibiotic resistance. If combined with the provision of clean water and sanitation, targeted hygiene can reduce the circulation of resistant bacteria in homes and communities, regardless of a country\u27s Human Development Index (overall social and economic development). Achieving a reduction of AMR strains in health care settings requires a mirrored reduction in the community. The authors call upon national and international policy makers, health agencies, and health care professionals to further recognize the importance of targeted hygiene in the home and everyday life settings for preventing and controlling infection, in a unified quest to tackle AMR

armA and Aminoglycoside Resistance in Escherichia coli

We report armA in an Escherichia coli pig isolate from Spain. The resistance gene was borne by self-transferable IncN plasmid pMUR050. Molecular analysis of the plasmid and of the armA locus confirmed the spread of this resistance determinant