A Bright Future for Antibiotics?

Abstract

Multidrug resistance is a global threat as the clinically available potent antibiotic drugs are becoming exceedingly scarce. For example, increasing drug resistance among gram-positive bacteria is responsible for approximately one-third of nosocomial infections. As ribosomes are a major target for these drugs, they may serve as suitable objects for novel development of next-generation antibiotics. Three-dimensional structures of ribosomal particles from Staphylococcus aureus obtained by X-ray crystallography have shed light on fine details of drug binding sites and have revealed unique structural motifs specific for this pathogenic strain, which may be used for the design of novel degradable pathogen-specific, and hence, environmentally friendly drugs.

A Global Overview of β-lactam Resistance Genes in Klebsiella pneumoniae

“…CTX-M enzymes, especially CTX-M-15, are related to various epidemiological situations and have spread throughout the continents due to epidemic plasmids and/or epidemic strains [47]. Corroborating this statement, in the present study, the bla CTX-M-15 gene was found in K. pneumoniae in all continents evaluated Table (1)(2)(3)(4). Many of the emerging antimicrobial resistance problems of the nineties have been characterized by difficulty in recognition of resistance in the laboratory, particularly by rapid susceptibilitytest methods.…”

“…This is responsible for a variety of diseases in humans and animals, such as urinary tract infection, pneumoniae, intra-abdominal infection, bloodstream infection, meningitis, pyogenic liver abscess and is a prominent nosocomial pathogen [1,2]. Moreover, the occurrence and global spread of hypervirulent and MDR (multidrug-resistant) K. pneumoniae are increasingly reported in communityacquired and nosocomial infections [3], and the use of antimicrobials in the treatment of infections has become progressively more difficult [4,5]. However, despite there has been an increase in the number of vulnerable populations to MDR pathogens, in addition to a renewed interest in the Klebsiella pneumoniae, many questions about this pathogen are still unknown, as to how resistance genes spread out and how they reach humans [6].…”

“…Over time, bacteria have developed several mechanisms by which they can withstand antimicrobials, rendering the action of these substances ineffective [3]. The resistance mechanisms of a gram-negative bacterium include: efflux pump; membrane permeability; production of β-lactamases; modification of antibiotic targets; and, acquisition of alternative metabolic pathways to those inhibited by the antibiotic [4,6]. One of the most important mechanisms of resistance in bacteria is the Extended Spectrum β-lactamase (ESBL) production [7].…”

Discovery of Small‐Molecule Antibiotics against a Unique tRNA‐Mediated Regulation of Transcription in Gram‐Positive Bacteria

“…Ribosomes have long been the target of clinically useful antibiotics. Differences found in bacterial and eukaryote ribosomes through high resolution three‐dimensional structural analysis could be exploited for next‐generation antibiotics …”

“…Differences found in bacterial and eukaryoter ibosomest hrough high resolution three-dimensional structural analysis could be exploited for next-generation antibiotics. [57] Riboswitches are ideal targets because analogueso fs mallmolecule metabolites can be used to disruptn ormal riboswitch regulation of the gene expression. Riboswitch inhibitors have been found.…”