Pulling the Brakes on Fast and Furious Multiple Drug-Resistant (MDR) Bacteria

Abstract

Life-threatening bacterial infections have been managed by antibiotics for years and have significantly improved the wellbeing and lifetime of humans. However, bacteria have always been one step ahead by inactivating the antimicrobial agent chemically or by producing certain enzymes. The alarming universal occurrence of multidrug-resistant (MDR) bacteria has compelled researchers to find alternative treatments for MDR infections. This is a menace where conventional chemotherapies are no longer promising, but several novel approaches could help. Our current review article discusses the novel approaches that can combat MDR bacteria: starting off with potential nanoparticles (NPs) that efficiently interact with microorganisms causing fatal changes in the morphology and structure of these cells; nanophotothermal therapy using inorganic NPs like AuNPs to destroy pathogenic bacterial cells; bacteriophage therapy against which bacteria develop less resistance; combination drugs that act on dissimilar targets in distinctive pathways; probiotics therapy by the secretion of antibacterial chemicals; blockage of quorum sensing signals stopping bacterial colonization, and vaccination against resistant bacterial strains along with virulence factors. All these techniques show us a promising future in the fight against MDR bacteria, which remains the greatest challenge in public health care.

Keywords: bacteriophages; combination therapy; multidrug resistance; nanoantibiotics; nanoparticles.

Figure 1

The possible ways a bacterium resists the action of an antibiotic drug.

Figure 2

A pictorial presentation of various strategies, targets and effector molecules that can be used to curb the multiple drug resistance in bacterial pathogens.

Figure 3

Different modes of action possible for the eradication (killing) of bacterial cells through silver (Ag) nanoparticles [1].

Figure 4

Mode of action (bactericidal effects) of AgNPs against bacteria against MRSA.

Figure 5

Promyelocytes in the bone marrow synthesize α-defensins. 94 amino acid preprodefensin (purple) is biosynthesized in the ribosomes; the 19 amino-acid N-terminal signal sequence is cleaved and it converted to a 75 amino-acid prodefensin (brown). Subsequent cleavage of residues generates a 29–30 amino acid mature defensin (green). During phagocytosis (pathogens), defensin-rich primary granules fuse with phagocytic vacuoles and high concentrations of defensins are generated.

Figure 6

Possible mechanisms antimicrobial peptides can kill bacterial superbugs.

Figure 7

Phage-derived antimicrobial techniques. Novel antimicrobial strategies derived from phages and their products. (a) Phages target specific bacterial pathogens and thus cause the lysis of that particular bacterial cell wall; (b) phages produce enzymes that target particular bacterial pathogens; (c) phages can be used to transfer antibiotic-sensitive genes into drug-resistant bacteria.

Figure 8

Mode of action of novel antibodies how they bind to multidrug-resistant (MDR) bacteria and present to macrophages and destroy them.

Figure 9

Quorum sensing can be blocked by producing and apply chemical analogs, which render the bacteria unable to communicate and hence pathogenicity-related expression is affected.