ESKAPE Pathogens: Looking at Clp ATPases as Potential Drug Targets

Abstract

Bacterial antibiotic resistance is rapidly growing globally and poses a severe health threat as the number of multidrug resistant (MDR) and extensively drug-resistant (XDR) bacteria increases. The observed resistance is partially due to natural evolution and to a large extent is attributed to antibiotic misuse and overuse. As the rate of antibiotic resistance increases, it is crucial to develop new drugs to address the emergence of MDR and XDR pathogens. A variety of strategies are employed to address issues pertaining to bacterial antibiotic resistance and these strategies include: (1) the anti-virulence approach, which ultimately targets virulence factors instead of killing the bacterium, (2) employing antimicrobial peptides that target key proteins for bacterial survival and, (3) phage therapy, which uses bacteriophages to treat infectious diseases. In this review, we take a renewed look at a group of ESKAPE pathogens which are known to cause nosocomial infections and are able to escape the bactericidal actions of antibiotics by reducing the efficacy of several known antibiotics. We discuss previously observed escape mechanisms and new possible therapeutic measures to combat these pathogens and further suggest caseinolytic proteins (Clp) as possible therapeutic targets to combat ESKAPE pathogens. These proteins have displayed unmatched significance in bacterial growth, viability and virulence upon chronic infection and under stressful conditions. Furthermore, several studies have showed promising results with targeting Clp proteins in bacterial species, such as Mycobacterium tuberculosis, Staphylococcus aureus and Bacillus subtilis.

Antarctic Marine Bacteria as a Source of Anti-Biofilm Molecules to Combat ESKAPE Pathogens

“…Consequently, there is an urgent need to develop new weapons to fight these pathogens, with particular emphasis on the eradication of their biofilms [31]. Several strategies are currently being explored in order to treat ESKAPErelated biofilms [2,32]. Despite this, there are no available molecules that are actually able to interfere with biofilm formation or promote biofilm disaggregation.…”

“…ESKAPE pathogens are mainly responsible for nosocomial infections, causing infections that are defined as hospital-acquired infections (HAIs) that affect patients within 48 h of hospital admission, 3 days after discharge, or 30 days after a surgical intervention [2]. Furthermore, ESKAPE pathogens are responsible for more than 40% of infections in intensive care units (ICUs) and require unaffordable economic expenses, especially in developing countries [3].…”

Advancing Antimicrobial Textiles: A Comprehensive Study on Combating ESKAPE Pathogens and Ensuring User Safety

“…Extensive research has been conducted to understand the mechanisms of resistance exhibited by ESKAPE pathogens and to explore alternative approaches, in combination with antibiotics, to reducing the health and cost implications of infectious diseases caused by these pathogens. These alternative approaches include bacteriophage therapy [6], usage of antimicrobial peptides [7], photodynamic therapy [8], usage of antibacterial antibodies [9,10], as well as the application of nanoparticles [5,[10][11][12] and phytochemicals [13]. Advanced porous materials, such as mesoporous silica nanoparticles, porous silicon nanoparticles, metal-organic frameworks, covalent-organic frameworks, hydrogen-bonded organic frameworks, and porous carbon materials, have also emerged as promising alternatives due to their low cost of production, high biocompatibility, adjustable porous structure, large surface area, and easy surface functionalization [14].…”

High oral carriage of multidrug resistant Gram-negative bacilli in adolescents: the SOPKARD-Junior study

“…Gram-negative bacilli such as Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter spp. is one of the most frequent causes of nosocomial infections belonging to the alarming ESKAPE group ( Paauw et al., 2009 ; Akbari et al., 2016 ; Motiwala et al., 2022 ).…”