Mammals' humoral immune proteins and peptides targeting the bacterial envelope: from natural protection to therapeutic applications against multidrug‐resistant Gram‐negatives

Abstract

Mammalian innate immunity employs several humoral ‘weapons’ that target the bacterial envelope. The threats posed by the multidrug‐resistant ‘ESKAPE’ Gram‐negative pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) are forcing researchers to explore new therapeutic options, including the use of these immune elements. Here we review bacterial envelope‐targeting (peptidoglycan and/or membrane‐targeting) proteins/peptides of the mammalian immune system that are most likely to have therapeutic applications. Firstly we discuss their general features and protective activity against ESKAPE Gram‐negatives in the host. We then gather, integrate, and discuss recent research on experimental therapeutics harnessing their bactericidal power, based on their exogenous administration and also on the discovery of bacterial and/or host targets that improve the performance of this endogenous immunity, as a novel therapeutic concept. We identify weak points and knowledge gaps in current research in this field and suggest areas for future work to obtain successful envelope‐targeting therapeutic options to tackle the challenge of antimicrobial resistance.

Bacterial virulence regulation through soluble peptidoglycan fragments sensing and response: knowledge gaps and therapeutic potential

“…Meanwhile, its excessive activation has been shown to cause aberrant morphology, division and growth defects, and increased susceptibility to lysis (Raivio et al 2013 , Bernal-Cabas et al 2015 , Delhaye et al 2016 ). In fact, the overactivation of this system has been demonstrated to be the initial mechanism through which the innate immunity’s PGN Recognition Proteins (PGLYRPs) are able to kill susceptible Gram-negative species (Torrens et al 2020 , Escobar-Salom et al 2022 ). More specifically, the overactivation of CpxAR caused by PGLYRPs derives in the induction of multiple stresses that result in membrane depolarization, blockade of cytosolic PGN, protein and nucleic acid synthesis, and massive production of hydroxyl radicals that are finally responsible for bacterial death (Kashyap et al 2011 , 2014 , 2017 ).…”

The Expression of Antibacterial Peptide Turgencin A in Pichia pastoris and an Analysis of Its Antibacterial Activity

“…They consist of between 10 and 50 amino acids and are now candidates for addressing the challenges associated with antibiotic resistance [ 8 , 9 ]. Antimicrobial peptides are derived from a wide range of sources, and as many as 3000 have been identified and isolated from mammals [ 10 ], amphibians [ 11 ], marine animals [ 12 ], insects [ 13 ], and plants [ 14 , 15 ]. Antimicrobial peptides can rupture bacteria by forming ion channels in cell membranes [ 16 ], piercing pores, and promoting membrane disintegration.…”

A review on contemporary nanomaterial-based therapeutics for the treatment of diabetic foot ulcers (DFUs) with special reference to the Indian scenario

“…With the increasing percentage of biofilm infections, it is necessary to develop non-commercial antimicrobial treatments, such as nanomaterials that possess intrinsic anti-biofilm properties by modulating their biophysical or biochemical parameters to cause removal and disruption of biofilms, such as synthesizing nanomaterials as drug delivery paradigms for carrying bioactive compounds, antibiotics, antioxidants, growth factors and stem cells to infection sites for better incursion through the biofilm matrix. 13 Nanomaterials can be used to treat chronic foot ulcers because they help in modulating biofilm formation and microbial colonization in wounds based on their different particle shapes, compositions, sizes and surface charges, resulting in alterations in the composition of the bacterial cell membrane and generation of reactive oxygen species (ROS), lipid peroxidation, loss of respiratory activity, nitrosation of cysteines and DNA unwinding of metabolic pathways. 14 Due to the heterogeneity of nanomaterials, they can serve as effective platforms to deliver anti-inflammatory, anti-biofilm and angiogenic properties based on the pathophysiological condition of the wound site.…”