The intrinsic resistome of bacterial pathogens

Abstract

Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyze recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice.

Genome Dynamics and Molecular Infection Epidemiology of Multidrug-Resistant Helicobacter pullorum Isolates Obtained from Broiler and Free-Range Chickens in India

“…Class J contains genes having functions related to translation, ribosomal structure, and biogenesis, while classes E and M consist of genes involved in amino acid transport/metabolism, and cell wall/envelope biogenesis, respectively. The core genome comprised genes encoding multidrug efflux pumps, which contribute to intrinsic drug resistance in bacteria (31). The genes encoding metallo-␤-lactamase enzymes that confer resistance to ␤-lactam antibiotics, including carbapenems, were also identified in the core genome.…”

Blocking Peptidoglycan Recycling in Pseudomonas aeruginosa Attenuates Intrinsic Resistance to Fosfomycin

“…In addition to the mechanisms that traditionally have been attributed to intrinsic resistance of P. aeruginosa, such as low permeability, efficient detoxification by efflux pumps, and antibiotic inactivation enzymes, recent studies indicate that intrinsic antibiotic resistance should be considered as an emergent systemic property rather than a specific adaptation to the presence of antibiotics. 1,17,29 In this vein, the novel cell wall recycling route in Pseudomonas sp. 8 provides a rationale for intrinsic resistance to fosfomycin, that is, the consequence of a unique metabolic pathway of cell wall sugar recovery in this organisms.…”

Cephem Potentiation by Inactivation of Nonessential Genes Involved in Cell Wall Biogenesis of β-Lactamase-Producing Escherichia coli

“…The antimicrobial susceptibility phenotype of a given bacterial species depends on the concerted activities of several elements, which as a whole are known as the intrinsic resistome (10,11). The various components of the Escherichia coli intrinsic resistome have been inferred by previous studies measuring the susceptibility and fitness of in-frame gene deletion mutants in the presence of antimicrobial agents (12,13).…”