Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches

Abstract

The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed by the emergence of resistance. The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics. Today, research is active in finding new treatments for multidrug-resistant pathogens. In a step to guide the efforts, the WHO has published a list of the most dangerous bacteria that are resistant to current treatments and requires the development of new antibiotics for combating the resistance. Among the list are various Gram-positive bacteria that are responsible for serious healthcare and community-associated infections. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and drug-resistant Streptococcus pneumoniae are of particular concern. The resistance of bacteria is an evolving phenomenon that arises from genetic mutations and/or acquired genomes. Thus, antimicrobial resistance demands continuous efforts to create strategies to combat this problem and optimize the use of antibiotics. This article aims to provide a review of the most critical resistant Gram-positive bacterial pathogens, their mechanisms of resistance, and the new treatments and approaches reported to circumvent this problem.

Anandamide alters the membrane properties, halts the cell division and prevents drug efflux in multidrug resistant Staphylococcus aureus

“…MRSA strains also possess the ability to constantly acquire additional antibiotic resistance genes, thereby creating difficult to treat superbugs 2,3 . There are several mechanisms responsible for the development of antibiotic resistance in S. aureus 4,5 . Among others, it may be caused by alterations of the target site resulting in reduced affinity to the antibiotics; presence of enzymes that modulate or inactivate the antibiotics; decreased uptake or enhanced efflux of the antibiotics resulting in suboptimal intracellular drug concentrations; or the bacteria are encapsulated in biofilms that reduce the bioavailability of the drugs [5][6][7][8] .The anti-bacterial effect of penicillin and other β-lactam antibiotics is achieved by inhibiting the enzymatic activity of the transpeptidase/transglycosylase enzyme penicillin-binding protein 2 (PBP2), which is involved in the last step of cell wall synthesis 9 .…”

“…However, resistance to methicillin rapidly developed that led to its discontinuation. The resistance to methicillin is due to the acquisition of a non-native gene (mecA) that encodes for the transpeptidase PBP2a showing low affinity for methicillin and other β-lactam antibiotics, thereby enabling cell wall synthesis in the presence of β-lactams 4,5,9 . The mecA gene is carried on a mobile genetic element termed staphylococcal chromosomal cassette (SCCmec) that also express the two genes mecR1 and mecI involved in the regulation of mecA 5 .…”

In vitro biofabrication of silver nanoparticles: Optimization, characterization, and activity against beta-lactamases-resistant Enterococcus faecalis

“…Therefore, future studies aimed at assessing and producing clinically feasible sources of AgNPs for in vivo studies are necessary to translate these ndings into clinical use. The correlation between the production of -lactamases and the spread of resistance among isolates of Gram-positive pathogens is very high, forming serious clinical challenges (Jubeh et al 2020). In particular, ESBLs (extended-spectrum beta-lactamases) are enzymes that deactivate β-lactam antibiotics by hydrolysis and have the ability to transfer bacterial resistance to the penicillins, rst-, second-, and third-generation cephalosporins (Santos et al 2020).…”

Carbapenems for the Treatment of Pneumonia: A literature review regarding resistance, risk factors, and mortality

“…The resistance of P. aeruginosa to aminoglycosides is caused by the Aminoglycoside Modifying Enzime (AME), which inactivates aminoglycosides by attaching phosphate, adenylyl or acetyl radicals to the antibiotic molecule, and decreases the binding affinity to its target in bacterial cells. 27 The mechanism of antibiotic resistance can be in various ways, including preventing access to antibiotics on the target: decreased permeability and increased antibiotic reflux, gene mutations: changing the target of antibiotics through gene mutations, direct modification of antibiotics: inactivation of antibiotics through enzymes from bacteria. 28 Based on various kinds of literature the resistance can be genotype or phenotype, the resistance mechanism of carbapenems is dominated by porin mutase, antibiotic inactivation by enzyme hydrolysis, increased efflux pump expression and mutase mediated by plasmid.…”