Biofilm and Small Colony Variants—An Update on Staphylococcus aureus Strategies toward Drug Resistance

Abstract

Recently, the drawbacks arising from the overuse of antibiotics have drawn growing public attention. Among them, drug-resistance (DR) and even multidrug-resistance (MDR) pose significant challenges in clinical practice. As a representative of a DR or MDR pathogen, Staphylococcus aureus can cause diversity of infections related to different organs, and can survive or adapt to the diverse hostile environments by switching into other phenotypes, including biofilm and small colony variants (SCVs), with altered physiologic or metabolic characteristics. In this review, we briefly describe the development of the DR/MDR as well as the classical mechanisms (accumulation of the resistant genes). Moreover, we use multidimensional scaling analysis to evaluate the MDR relevant hotspots in the recent published reports. Furthermore, we mainly focus on the possible non-classical resistance mechanisms triggered by the two important alternative phenotypes of the S. aureus, biofilm and SCVs, which are fundamentally caused by the different global regulation of the S. aureus population, such as the main quorum-sensing (QS) and agr system and its coordinated regulated factors, such as the SarA family proteins and the alternative sigma factor σB (SigB). Both the biofilm and the SCVs are able to escape from the host immune response, and resist the therapeutic effects of antibiotics through the physical or the biological barriers, and become less sensitive to some antibiotics by the dormant state with the limited metabolisms.

Preparation, Characterization, and Staphylococcus aureus Biofilm Elimination Effect of Baicalein-Loaded β-Cyclodextrin-Grafted Chitosan Nanoparticles

“…It is estimated that over 60% of treated bacterial infections arise from biofilm in developed countries. 9 Thus, infections of medical devices caused by S. aureus colonization with the formation of biofilm are becoming a common and serious problem in hospital-infected patients. 10 , 11 There is an urgent need to develop novel anti-biofilm formulation to overcome the drug resistance problem caused by the bacterial biofilm.…”

Whole-Genome Sequence of Multidrug-Resistant Methicillin-Resistant Staphylococcus epidermidis Carrying Biofilm-Associated Genes and a Unique Composite of SCCmec

“…Antibiotics 2022, 11, 861 2 of 15 MDR staphylococci can survive in hostile environments by forming biofilms or switching into small colony variants (SCVs) [1]. The genetic plasticity of Staphylococcal species has aided in the emergence of several drug-resistant strains, posing a significant therapeutic problem [5].…”

“…In the past decades, antibiotics have played a crucial role in fighting microbial infections. However, the overuse of antibiotics in clinical practice poses a serious risk to the public, and contributes to the emergence of multidrug-resistant (MDR) Staphylococcus aureus , which is responsible for various persistent and chronic infections [ 1 ]. Methicillin-resistant S. epidermidis (MRSE) is classified as a pathogen related to nosocomial and community-acquired infections [ 2 ].…”

“…The failure of antibiotic therapy may be linked to the accumulation of resistance-relevant genes, as well as the flexibility changes in bacterial phenotypes [ 4 ]. MDR staphylococci can survive in hostile environments by forming biofilms or switching into small colony variants (SCVs) [ 1 ]. The genetic plasticity of Staphylococcal species has aided in the emergence of several drug-resistant strains, posing a significant therapeutic problem [ 5 ].…”

Evaluation of the Antibiotic Resistance Pattern at the Medical Services Administration Hospital in Khartoum, Sudan, 2021

“…Figure 6: The number of resistant cases of S. aureus to the assessed antibiotics.Staphylococcus aureus shows the adaptive evolution of bacteria in the antibiotic era better than any other human pathogen. It has a unique ability to quickly adapt to each new antibiotic, from penicillin and methicillin to the most recent ones, linezolid and daptomycin(Guo et al 2022;Silva et al 2022).The mechanisms of S. aureus resistance include enzymatic inactivation of the antibiotic (penicillinase and aminoglycoside-modification enzymes); alteration of the target with decreased affinity for the antibiotic (notable examples being penicillin-binding protein 2a of methicillin-resistant S. aureus and D-Ala-D-Lac of peptidoglycan precursors of vancomycin-resistant strains), trapping of the antibiotic (for vancomycin and possibly daptomycin) and efflux pumps (fluoroquinolones and tetracycline)(Peterson and Kaur 2018).Complex genetic arrays (staphylococcal chromosomal cassette mec elements or the vanA operon) have been acquired by S. aureus through horizontal gene transfer, while resistance to other antibiotics, including some of the most recent ones (e.g., fluoroquinolones, linezolid, and daptomycin), has developed through spontaneous mutations and positive selection. Detection of the resistance mechanisms and their genetic basis is an important support for antibiotic susceptibility surveillance in S. aureus(Partridge et al 2018; Gheorghe, Popa, and Măruţescu 2018).…”