Bacteriophage therapy against ESKAPE bacterial pathogens: Current status, strategies, challenges, and future scope.

The ESKAPE pathogens are the primary threat due to their constant spread of drug resistance worldwide. These pathogens are also regarded as opportunistic pathogens and could potentially cause nosocomial infections. Most of the ESKAPE pathogens have developed resistance to almost all the antibiotics that are used against them. Therefore, to deal with antimicrobial resistance, there is an urgent requirement for alternative non-antibiotic strategies to combat this rising issue of drug-resistant organisms. One of the promising alternatives to this scenario is implementing bacteriophage therapy. This under-explored mode of treatment in modern medicine has posed several concerns, such as preferable phages for the treatment, impact on the microbiome (or gut microflora), dose optimisation, safety, etc. The review will cover a rationale for phage therapy, clinical challenges, and propose phage therapy as an effective therapeutic against bacterial coinfections during pandemics. This review also addresses the expected uncertainties for administering the phage as a treatment against the ESKAPE pathogens and the advantages of using lytic phage over temperate, the immune response to phages, and phages in combinational therapies. The interaction between bacteria and bacteriophages in humans and countless animal models can also be used to design novel and futuristic therapeutics like personalised medicine or bacteriophages as anti-biofilm agents. Hence, this review explores different aspects of phage therapy and its potential to emerge as a frontline therapy against the ESKAPE bacterial pathogen.

Different Efflux Pump Systems in Acinetobacter baumannii and Their Role in Multidrug Resistance.

Several infections, such as pneumonia, urinary tract infections (UTIs), as well as bloodstream, skin, and soft tissue infections, are caused by Acinetobacter baumannii, a nosocomial pathogen and Gram-negative coccobacillus. Due to its resistance to a variety of medications, multidrug therapy, and occasionally pan therapies, this bacterium is a huge public health concern. Drug resistance is a big worry not only in A. baumannii, but it is also a major challenge in many other diseases. Antibiotic resistance, biofilm development, and genetic alterations are all linked to variables like the efflux pump. Efflux pumps are transport proteins involved in the extrusion of hazardous substrates from within cells into the external environment (including nearly all types of therapeutically relevant antibiotics). Both Gram-positive and Gram-negative bacteria, as well as eukaryotic organisms, contain these proteins. Efflux pumps may be specialized for a single substrate or can transport a variety of structurally dissimilar molecules (including antibiotics of many classes); these pumps have been linked to multiple drug resistance (MDR). There are five primary families of efflux transporters in the prokaryotic kingdom: MF (major facilitator), MATE (multidrug and toxic efflux), RND (resistance-nodulation-division), SMR (small multidrug resistance), and ABC (ATP-binding cassette). The efflux pumps and their types as well as the mechanisms of an efflux pump involved in multidrug resistance in bacteria have been discussed here. The main focus is on the variety of efflux pumps commonly found in A. baumannii, along with their mechanism by which they make this bacteria drug resistant. The efflux-pump-inhibitor-based strategies that are significant in targeting efflux pumps in A. baumannii have also been discussed. The connection of biofilm and bacteriophage with the efflux pump can prove as an efficient strategy for targeting efflux-pump-based resistance in A. baumannii.

Recent advances to combat ESKAPE pathogens with special reference to essential oils.

Biofilm-associated bacteria, especially ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), are a serious challenge worldwide. Due to the lack of discovery of novel antibiotics, in the past two decades, it has become necessary to search for new antibiotics or to study synergy with the existing antibiotics so as to counter life-threatening infections. Nature-derived compounds/based products are more efficient than the chemically synthesized ones with less resistance and lower side effects. In this descriptive review, we discuss the most promising therapeutics for the treatment of ESKAPE-related biofilms. The first aspect includes different types of natural agents [botanical drugs, essential oils (EOs), antimicrobial peptides, bacteriophages, and endolysins] effective against ESKAPE pathogens. The second part of the review deals with special references to EOs/essential oil components (EOCs) (with some exclusive examples), mode of action (via interfering in the quorum-sensing pathways, disruption of biofilm and their inhibitory concentrations, expression of genes that are involved, other virulence factors), existing in literature so far. Moreover, different essential oils and their major constituents were critically discussed using in vivo models to target ESKAPE pathogens along with the studies involving existing antibiotics.