The Mechanism of Bacterial Resistance and Potential Bacteriostatic Strategies

Abstract

Bacterial drug resistance is rapidly developing as one of the greatest threats to human health. Bacteria will adopt corresponding strategies to crack the inhibitory effect of antibiotics according to the antibacterial mechanism of antibiotics, involving the mutation of drug target, secreting hydrolase, and discharging antibiotics out of cells through an efflux pump, etc. In recent years, bacteria are found to constantly evolve new resistance mechanisms to antibiotics, including target protective protein, changes in cell morphology, and so on, endowing them with multiple defense systems against antibiotics, leading to the emergence of multi-drug resistant (MDR) bacteria and the unavailability of drugs in clinics. Correspondingly, researchers attempt to uncover the mystery of bacterial resistance to develop more convenient and effective antibacterial strategies. Although traditional antibiotics still play a significant role in the treatment of diseases caused by sensitive pathogenic bacteria, they gradually lose efficacy in the MDR bacteria. Therefore, highly effective antibacterial compounds, such as phage therapy and CRISPER-Cas precision therapy, are gaining an increasing amount of attention, and are considered to be the treatments with the moist potential with regard to resistance against MDR in the future. In this review, nine identified drug resistance mechanisms are summarized, which enhance the retention rate of bacteria under the action of antibiotics and promote the distribution of drug-resistant bacteria (DRB) in the population. Afterwards, three kinds of potential antibacterial methods are introduced, in which new antibacterial compounds exhibit broad application prospects with different action mechanisms, the phage therapy has been successfully applied to infectious diseases caused by super bacteria, and the CRISPER-Cas precision therapy as a new technology can edit drug-resistant genes in pathogenic bacteria at the gene level, with high accuracy and flexibility. These antibacterial methods will provide more options for clinical treatment, and will greatly alleviate the current drug-resistant crisis.

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“…The therapeutic paradigm changed with the introduction of antibiotics into clinical use [ 1 , 2 ] which have continued to save lives around the globe [ 3 ]. Sadly, these gains are challenged globally with one of the greatest public health issues of our time, antibiotic resistance [ [3] , [4] , [5] ].…”

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“…Currently, methods for increasing human immunity to resist exogenous agents such as pathogenic microorganisms are being sought [ 1 , 2 ]. At the same time, there has recently been growing concern about anthropozoonoses.…”

Chlorella minutissima-assisted silver nanoparticles synthesis and evaluation of its antibacterial activity

“…It has been predicted that by 2025, deaths caused by AMR will be more than deaths caused by cancer [ 2 ]. Pathogens have developed various resistance mechanisms such as alteration of the target molecules, active efflux of the antimicrobial agents from the bacterial cells, modification of the antimicrobial agents, decreased penetration of the antimicrobial agents into the bacterial cells, degradation of antimicrobial agents and resistance due to global adaptation [ 3 , 4 , 5 ]. Events such as horizontal gene transfer and conjugation also leads to the transfer of resistant genes among the bacterial species leading to widespread resistance against the existing antimicrobial agents [ 6 ].…”