Mechanisms of methicillin resistance in staphylococci

Abstract

The continuously high prevalence of methicillin‐resistant staphylococci (MRS) throughout the world is a constant threat to public health, owing to the multiresistant characteristics of these bacteria. Methicillin resistance is phenotypically associated with the presence of the penicillin‐binding protein 2a (PBP2a) not present in susceptible staphylococci. This protein has a low binding affinity for β‐lactam antibiotics. It is a transpeptidase which may take over cell wall synthesis during antibiotic treatment when normally occurring PBPs are inactivated by ligating β‐lactams. PBP2a is encoded by the mecA gene, which is located in mec, a foreign DNA region. Expression of PBP2a is regulated by proteins encoded by the plasmid‐borne blaR1‐blaI inducer‐repressor system and the corresponding genomic mecR1‐mecI system. The blaR1‐blaI products are important both for the regulation of β‐lactamase and for mecA expression. Methicillin resistance is influenced by a number of additional factors, e.g. the products of the chromosomal fem genes which are important in the synthesis of normal peptidoglycan precursor molecules. Inactivation of fem‐genes results in structurally deficient precursors which are not accepted as cell wall building blocks by the ligating PBP2a transpeptidase during antibiotic treatment. This may result in reduced resistance to β‐lactam antibiotics. Inactivation of genes affecting autolysis has shown that autolytic enzymes are also of importance in the expression of methicillin resistance. Methicillin resistance has evolved among earth microorganisms for protection against exogenous or endogenous antibiotics. Presumably the mec region was originally transferred from coagulase negative staphylococci (CNS) to Staphylococcus aureus (SA). A single or a few events of this kind with little subsequent interspecies transfer had been anticipated. However, recent data suggest a continuous horizontal acquisition by S. aureus of mec, being unidirectional from CNS to SA. Methicillin resistance may also be associated with mechanisms independent of mecA, resulting in borderline methicillin resistance. These mechanisms include β‐lactamase hyperproduction, production of methicillinases, acquisition of structurally modified normal PBPs, or the appearance of small colony variants of SA. Most MRS are multiresistant, and the mec region may harbour several resistance determinants, resulting in a clustering of resistance genes within this region.

Antibiotic resistance of staphylococci from humans, food and different animal species according to data of the Hungarian resistance monitoring system in 2001

“…Strains of methicillin-resistant staphylococci are able to produce another type of PBP, namely PBP2a that requires 2-10 times higher penicillin concentrations for inactivation than PBP2 and 20 times higher than PBP1. PBP2a may take over as a transpeptidase for continued peptidoglycan synthesis at methicillin concentrations which inhibit the normal PBPs (Brakstad and Maeland, 1997).…”

Species identification, slime production and oxacillin susceptibility in coagulase-negative staphylococci isolated from nosocomial specimens

“…[6], stethoscopes [6], beds [9], tables for nursing elements [3], oxigen tube extreme [1], and oxigen mask [1]. These surfaces may play an important role in the spread of infectious agents including antimicrobial-resistant strains, so the regular use of disinfectant for their cleaning is advisable.…”

“…Others mechanisms associated with oxacillin (methicillin) resistance do not involve the mecA gene. These mechanisms may include hyperproduction of β-lactamase, production of penicillin-binding proteins other than PBP2a encoded by mecA, enzymes which inactivate methicillin or unknown mechanisms (3). Detection of resistance to oxacillin in staphylococci is important to guide the therapy and prevent the patient from being unnecessarily treated with vancomycin, which is an antimicrobial agent that presents therapeutic complications, high costs, and may lead to the selection of resistant mutants (19).…”

Resistance to methicillin of coagulase-negative staphylococci (CNS) isolated from bovine mastitis

“…One of the mechanisms of staphylococcal resistance to β-lactam antibiotics is the production of enzymes (β-lactamases) which, due to hydrolysis, break the β-lactam ring forming the inactive product (Brakstad andMaeland 1997, Bartoszewicz-Potyrała andPrzondo-Mordarska 2002). Staphylococcal resistance to β-lactam antibiotics is mainly mediated by the synthesis of the altered form of penicillin-binding protein 2 (called PBP2a or PBP2') of reduced affinity for β-lactam antibiotics.…”