Innovative Strategies to Overcome Antimicrobial Resistance and Tolerance

Abstract

Antimicrobial resistance and tolerance are natural phenomena that arose due to evolutionary adaptation of microorganisms against various xenobiotic agents. These adaptation mechanisms make the current treatment options challenging as it is increasingly difficult to treat a broad range of infections, associated biofilm formation, intracellular and host adapted microbes, as well as persister cells and microbes in protected niches. Therefore, novel strategies are needed to identify the most promising drug targets to overcome the existing hurdles in the treatment of infectious diseases. Furthermore, discovery of novel drug candidates is also much needed, as few novel antimicrobial drugs have been introduced in the last two decades. In this review, we focus on the strategies that may help in the development of innovative small molecules which can interfere with microbial resistance mechanisms. We also highlight the recent advances in optimization of growth media which mimic host conditions and genome scale molecular analyses of microbial response against antimicrobial agents. Furthermore, we discuss the identification of antibiofilm molecules and their mechanisms of action in the light of the distinct physiology and metabolism of biofilm cells. This review thus provides the most recent advances in host mimicking growth media for effective drug discovery and development of antimicrobial and antibiofilm agents.

The Activity of Nourseothricin Against Drug-Resistant Bacteria

“…Because this strategy makes it more difficult for bacteria to build resistance, it could be a useful solution to address the growing problem of antibiotic-resistant illnesses. [24] In vitro experiments have shown that nourseothricin is effective against a variety of multidrug resistant bacterial infections. According to Drepper et al's (2010) investigation, nourseothricin was efficient against pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative bacteria that evolved an ESBL.…”

“…Because it has the potential to overcome single-drug resistance processes, nourseothricin's ability to boost the effectiveness of other antibiotics is a viable technique for treating multidrug-resistant infections. [24] Nourseothricin has some potential activity, but there are a few issues that must be addressed before it can be used in clinical trials. Understanding a medication's pharmacokinetics and safety profile is critical for selecting safe and effective dose regimens and a course of therapy.…”

Horizontal Gene Transfer of Antibiotic Resistance Genes in Biofilms

“…A recent study from Lozano et al described a simple biofilm model of human sputum to test the sensibility of P. aeruginosa strains against different antibiotics [72]. The development of specific growth media to better mimic in vivo biofilm formation and new biofilm antimicrobial susceptibility tests could contribute to the reduction in treatment failure [74][75][76].…”

Whole Genome Sequencing and Phenotypic Analysis of Antibiotic Resistance in Filifactor alocis Isolates

“…Nevertheless, little is known of its antimicrobial resistance (AMR) properties [ 22 ]. Given that most infections still need antimicrobials to resolve successfully [ 23 ], it seems crucial to have updated and thorough information regarding the levels of AMR as well as the genetic determinants that might confer such resistance. Therefore, the phenotypic resistance levels of F. alocis isolates, obtained from subgingival samples of patients with different oral diseases, were tested.…”