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.

https://www.mdpi.com/2079-6382/11/9/1215/pdf?version=1662629214

The Mechanism of Bacterial Resistance and Potential Bacteriostatic Strategies

Plants in nature are under the persistent intimidation of severe microbial diseases, threatening a sustainable food production system. Plant-bacterial pathogens are a major concern in the contemporary era, resulting in reduced plant growth and productivity. Plant antibiotics and chemical-based bactericides have been extensively used to evade plant bacterial diseases. To counteract this pressure, bacteria have evolved an array of resistance mechanisms, including innate and adaptive immune systems. The emergence of resistant bacteria and detrimental consequences of antimicrobial compounds on the environment and human health, accentuates the development of an alternative disease evacuation strategy. The phage cocktail therapy is a multidimensional approach effectively employed for the biocontrol of diverse resistant bacterial infections without affecting the fauna and flora. Phages engage a diverse set of counter defense strategies to undermine wide-ranging anti-phage defense mechanisms of bacterial pathogens. Microbial ecology, evolution, and dynamics of the interactions between phage and plant-bacterial pathogens lead to the engineering of robust phage cocktail therapeutics for the mitigation of devastating phytobacterial diseases. In this review, we highlight the concrete and fundamental determinants in the development and application of phage cocktails and their underlying mechanism, combating resistant plant-bacterial pathogens. Additionally, we provide recent advances in the use of phage cocktail therapy against phytobacteria for the biocontrol of devastating plant diseases.

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Deploying Viruses against Phytobacteria: Potential Use of Phage Cocktails as a Multifaceted Approach to Combat Resistant Bacterial Plant Pathogens

Acinetobacter baumannii is a multidrug-resistant and invasive pathogen associated with the etiopathology of both an increasing number of nosocomial infections and is of relevance to poultry production systems. Multidrug-resistant Acinetobacter baumannii has been reported in connection to severe challenges to clinical treatment, mostly due to an increased rate of resistance to carbapenems. Amid the possible strategies aiming to reduce the insurgence of antimicrobial resistance, phage therapy has gained particular importance for the treatment of bacterial infections. This review summarizes the different phage-therapy approaches currently in use for multiple-drug resistant Acinetobacter baumannii, including single phage therapy, phage cocktails, phage–antibiotic combination therapy, phage-derived enzymes active on Acinetobacter baumannii and some novel technologies based on phage interventions. Although phage therapy represents a potential treatment solution for multidrug-resistant Acinetobacter baumannii, further research is needed to unravel some unanswered questions, especially in regard to its in vivo applications, before possible routine clinical use.

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Recent Progress in Phage Therapy to Modulate Multidrug-Resistant Acinetobacter baumannii, including in Human and Poultry

In the recent decades, antibiotic resistance has emerged and spread rapidly among clinically relevant pathogens. The natural ability of bacteria to transmit resistance determinants through horizontal gene transfer poses constant challenges to drug development. Natural molecules produced by soil microorganisms continue to be a key source of new antimicrobial agents. In this context, bacteria from the Geobacillus and Parageobacillus genera deserve special attention. Although there is commercial and industrial interest in these microorganisms, the full range of antibacterial compounds biosynthesized by the Geobacillus and Parageobacillus species remains largely unexplored. The aim of this review is to present the strong antimicrobial potential of these bacteria and endolysins produced by their bacteriophages.

/pdf/antimicrobial-potential-of-the-genera-geobacillus-and-27pf95qi.pdf

Antimicrobial Potential of the Genera Geobacillus and Parageobacillus, as Well as Endolysins Biosynthesized by Their Bacteriophages

Multi-drug resistance has called for a race to uncover alternatives to existing antibiotics. Phage therapy is one of the explored alternatives, including the use of endolysins, which are phage-encoded peptidoglycan hydrolases responsible for bacterial lysis. Endolysins have been extensively researched in different fields, including medicine, food, and agricultural applications. While the target specificity of various endolysins varies greatly between species, this current review focuses specifically on streptococcal endolysins. Streptococcus spp. causes numerous infections, from the common strep throat to much more serious life-threatening infections such as pneumonia and meningitis. It is reported as a major crisis in various industries, causing systemic infections associated with high mortality and morbidity, as well as economic losses, especially in the agricultural industry. This review highlights the types of catalytic and cell wall-binding domains found in streptococcal endolysins and gives a comprehensive account of the lytic ability of both native and engineered streptococcal endolysins studied thus far, as well as its potential application across different industries. Finally, it gives an overview of the advantages and limitations of these enzyme-based antibiotics, which has caused the term enzybiotics to be conferred to it.

/pdf/endolysins-against-streptococci-as-an-antibiotic-alternative-1mrgd3wm.pdf

Endolysins against Streptococci as an antibiotic alternative

Antimicrobial resistance (AMR) is a global crisis for human public health which threatens the effective prevention and control of ever-increasing infectious diseases. The advent of pandrug-resistant bacteria makes most, if not all, available antibiotics invalid. Meanwhile, the pipeline of novel antibiotics development stagnates, which prompts scientists and pharmacists to develop unconventional antimicrobials. Bacteriophage-derived endolysins are cell wall hydrolases which could hydrolyze the peptidoglycan layer from within and outside of bacterial pathogens. With high specificity, rapid action, high efficiency, and low risk of resistance development, endolysins are believed to be among the best alternative therapeutic agents to treat multidrug resistant (MDR) bacteria. As of now, endolysins have been applied to diverse aspects. In this review, we comprehensively introduce the structures and activities of endolysins and summarize the latest application progress of recombinant endolysins in the fields of medical treatment, pathogen diagnosis, food safety, and agriculture.

Qingqing Sun

Papers

Endolysin, a Promising Solution against Antimicrobial Resistance.