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Silva, V.;  Araújo, S.;  Monteiro, A.;  Eira, J.;  Pereira, J.E.;  Maltez, L.;  Igrejas, G.;  Lemsaddek, T.S.;  Poeta, P. Methicillin-Resistant Staphylococci. Encyclopedia. Available online: https://encyclopedia.pub/entry/40233 (accessed on 11 December 2025).
Silva V,  Araújo S,  Monteiro A,  Eira J,  Pereira JE,  Maltez L, et al. Methicillin-Resistant Staphylococci. Encyclopedia. Available at: https://encyclopedia.pub/entry/40233. Accessed December 11, 2025.
Silva, Vanessa, Sara Araújo, Andreia Monteiro, José Eira, José Eduardo Pereira, Luís Maltez, Gilberto Igrejas, Teresa Semedo Lemsaddek, Patricia Poeta. "Methicillin-Resistant Staphylococci" Encyclopedia, https://encyclopedia.pub/entry/40233 (accessed December 11, 2025).
Silva, V.,  Araújo, S.,  Monteiro, A.,  Eira, J.,  Pereira, J.E.,  Maltez, L.,  Igrejas, G.,  Lemsaddek, T.S., & Poeta, P. (2023, January 16). Methicillin-Resistant Staphylococci. In Encyclopedia. https://encyclopedia.pub/entry/40233
Silva, Vanessa, et al. "Methicillin-Resistant Staphylococci." Encyclopedia. Web. 16 January, 2023.
Methicillin-Resistant Staphylococci
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This entry is adapted from the peer-reviewed paper 10.3390/microorganisms11010124

Staphylococcus aureus, in particular methicillin-resistant S. aureus (MRSA), can cause a variety of infections from superficial skin and soft tissue infections to life-threatening septicaemia. S. aureus represents a serious public health problem in hospital and community settings, as well as an economic and animal welfare problem.

Staphylococcus aureus MRSA LA-MRSA

1. Staphylococci—An Overview

Staphylococci are Gram-positive cocci-shaped cells arranged in irregular clusters similar to grape clusters [1]. Although S. aureus is the major bacterium of its genus, more than 50 Staphylococcus species are registered in the List of Prokaryotic Names with Standing in Nomenclature database [2]. These bacteria are facultative anaerobes, catalase positive and salt (NaCl) tolerant [3]. The Staphylococcus genus is divided in two main groups, the coagulase-negative staphylococci (CoNS) and coagulase-positive staphylococci (CoPS). Staphylococcus species were first characterized by Friedrich Rosenbach, who established that yellow/orange colonies corresponded to CoPS species and white colonies to CoNS [4]. In general, staphylococci are natural inhabitants of skin and mucous membranes of human beings and animals, while the prevalence of species varies widely according to the host [2]. However, they can cause various types of infections ranging from skin infections to severe infections like necrotizing pneumonia or sepsis [5]. Staphylococci tolerate a wide range of temperatures, from 7 to 40 ℃, and survive under unfavourable conditions like dryness and dehydration, making them a persistent and widespread pathogen in the environment [3]. Among Staphylococci, Staphylococcus aureus and Staphylococcus epidermidis are the most frequently isolated species of the CoPS and CoNS groups, respectively, which is why S. epidermidis is the species most focused on in CoNS studies [4]. Staphylococcus aureus has been the major pathogen associated with nosocomial infections in humans [1]. However, more recently, infections caused by CoNS like S. epidermidis, S. haemolyticus and S. saprophyticus have emerged in hospitals [6]. Moreover, although to a lesser extent, CoNS are known to colonize both farm and domestic animals. For instance, several bovine mastitis infections associated with CoNS have increasingly been reported over the years [7][8][9]. CoNS have also been detected as contaminants in food products [10][11][12][13] becoming more frequent and harmful to both animals and humans, affecting public health and taking a huge economic burden.

2. Methicillin-Resistant Staphylococci

Penicillin is an antibiotic in the β-lactam family. It was introduced in clinical practice in 1941 and, only a year later, penicillin resistance in S. aureus was described. Ten years later, more than half of the isolates in large hospitals were already resistant to penicillin [14]. The need to create compounds resistant to the action of β-lactamases produced by staphylococci led to the development of other antimicrobials such as methicillin. However, shortly after the introduction of this antibiotic, methicillin-resistant S. aureus (MRSA) was isolated [15]. MRSA is now recognized as a high-priority pathogen according to the World Health Organization (WHO), since an emergence of these strains has been observed [16]. The mechanism of resistance to methicillin is based on the synthesis of a new penicillin-binding protein (PBP), the PBP2a, with little affinity for methicillin and other β-lactams, which blocks the arrival of the antibiotic at its target site and thus creates resistance [17]. The mecA gene is the main gene responsible for resistance to methicillin. This gene is found on the genetic loci called staphylococcal cassette chromosome mec (SCCmec). The expression of the mecA gene depends on two genes, mecR1, which regulates transcription, and mecI, which encodes the repressor protein [18]. There are two other mechanisms that result in weak resistance to methicillin and oxacillin in which the presence of the mecA gene is not clear. Strains with modifications in the affinity of PBP 1, 3, and 4 exhibit weak resistance to methicillin, and strains that hyper-produce β-lactamases have a limited resistance to oxacillin [19]. Although the mecA gene is the most common PBP2a-encoding gene, recently, the detection of a new mec gene was reported. mecC is part of the SCCmec type XI and has been detected in both S. aureus and CoNS in animal and environmental samples [20][21]. Two less frequent mec genes have been described, mecB and mecD, both detected in Macrococcus caseolyticus, although the mecB gene has been recently reported in S. aureus [22][23].
Staphylococcus spp. have the ability to quickly acquire resistance to antibiotics. This started with the first strains resistant to penicillin reported a few years after its introduction. The successive introduction of other antibiotics, such as macrolides, tetracycline, and chloramphenicol, had a similar result: that is, the rapid appearance of resistant strains which, in turn, led to the proliferation and dissemination of bacteria with a broad spectrum of resistance and a remarkable ability to survive in different environments [24][25]. One interesting fact about most of these strains is that they are generally resistant to β-lactams [26]. Different species have a wide range of antibiotic resistances and monoresistant and multiresistant strains have been found in the environment, in particular in the aquatic environment [27].

2.1. Mechanisms of Antibiotic Resistance in S. aureus

Antimicrobials are substances that inhibit or eliminate the growth of microorganisms and are therefore commonly used in the treatment and prevention of infections. They can be classified as bactericidal or bacteriostatic. Bactericidal drugs act by directly eliminating the microorganism, while bacteriostatic drugs inhibit bacterial growth and multiplication [28]. Among the main groups of bactericidal antibiotics are aminoglycosides, β-lactams, fluoroquinolones, and glycopeptides, while lincosamides, oxazolidinones, and macrolides are some of the drugs with bacteriostatic action [29].
Bacterial resistance to antimicrobials can be manifested through several mechanisms such as inhibition of cell wall synthesis, inhibition of cytoplasmic membrane synthesis or damage, inhibition of protein synthesis in ribosomes, changes in the synthesis of nucleic acids, and alteration of cellular metabolisms [30]. The resistance of bacteria to antibiotics can have an intrinsic typology, depending a lot on the typical and specific biology of the bacterium, or extrinsic, through horizontal gene transfer, where there is the acquisition of new genes, transported by plasmids, transposons, integrons, or bacteriophages, also known as phages [31].
Genetic alterations promoted by the mechanisms described here may provide bacteria with the ability to carry out certain biochemical mechanisms such as: enzymatic inactivation, efflux pumps, or target modification which can be specific for different classes of antimicrobials, as shown in Table 1 [32][33].
Table 1. Mechanisms of action and resistance of the most important classes of antibiotics.
Class of Antibiotics Mechanisms of Action Mechanisms of Resistance
Penicillins Inhibition of cell wall biosynthesis. Production of β-lactamases; PBP’s changed; efflux pumps.
Cephalosporins
Aminoglycosides Inhibition of protein synthesis by binding to the 30S ribosomal subunit. efflux pumps; modification of the target (ribosome).
Macrolides
Lincosamides Inhibition of protein synthesis by binding to the 30S ribosomal subunit. Modification of the target (ribosome).
Quinolones Inhibition of DNA synthesis. Target modification (DNA gyrase and DNA topoisomerase).
Tetracyclines Inhibition of protein synthesis at the level of peptide elongation. Efflux pumps; modification of the target (ribosome).
Phenicols Inhibition of the peptidyltransferase reaction in the 50S ribosomal subunit. efflux pumps; target modification (enzyme and ribosome).
Sulfonamides Inhibition of folic acid synthesis. Target modification (enzymes).

2.2. Virulence Factors in S. aureus

S. aureus is one of the first pathogens described and remains one of the most common causes of life-threatening infections of the bloodstream, skin, soft tissues, and even the lower respiratory tract, and serious deep-seated infections such as endocarditis, mastitis, and osteomyelitis [34]. The degree of pathogenicity of S. aureus depends on several components of the bacterial surface and extracellular proteins. The expression of most virulence factors in S. aureus is controlled by the agr locus (accessory gene regulator) which encodes a two-component signaling pathway whose activation ligand is a bacterial density sensor peptide (autoinducer peptide) which is also encoded by agr [35]. Thus, the agr system is directly involved in controlling the expression of virulence factors in S. aureus [35].
Four hemolysins have been identified: alpha, beta, gamma, and delta. They have hemolytic and cytolytic capacity and act on some cells of the host such as macrophages, leukocytes and fibroblasts. α-hemolysin is the most studied. It is responsible for the hemolysis zone observed around the S. aureus colonies and has its effect on eukaryotic cell membranes and erythrocytes. β-hemolysin is an active sphingomyelinase that acts on different cells, and γ and δ hemolysins, found in some strains of S. aureus, have the ability to lyse a variety of different cells [36]. Only 5–10% of S. aureus produce exfoliative toxins. Two serotypes of exfoliative toxins have been reported, A and B, which are biochemically and immunologically different, but with similar biological functions [37]. Exfoliative toxin A is chromosomal encoded whereas B is plasmid encoded. Both have proteolytic activity, dissolve the mucopolysaccharide matrix of the epidermis, and act as superantigens [38]. Enterotoxins are responsible for food poisoning with emesis and enterocolitis symptoms and are produced by 30–50% of S. aureus strains [39]. Toxic shock toxin is a thermostable protein synthesized by chromosomal genes. They are considered superantigens since they are capable of producing the massive proliferation of T lymphocytes and thus the production of cytokines, which leads to toxic shock syndrome [38]. Panton–Valentine’s leucocidin is a cytolytic toxin and is formed by two proteins, LukS-PV and LukF-PV, which form pores across the membrane of leukocytes causing efflux of the cell content, leading to lysis [40].

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Subjects: Microbiology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Vanessa Silva , Sara Araújo , Andreia Monteiro , José Eira , José Eduardo Pereira , Luís Maltez , Gilberto Igrejas , Teresa Semedo Lemsaddek , Patricia Poeta
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Update Date: 17 Jan 2023
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