Antibiotic Production and Antibiotic Resistance: The Two Sides of AbrB1/B2, a Two-Component System of Streptomyces coelicolor

Abstract

Antibiotic resistance currently presents one of the biggest threats to humans. The development and implementation of strategies against the spread of superbugs is a priority for public health. In addition to raising social awareness, approaches such as the discovery of new antibiotic molecules and the elucidation of resistance mechanisms are common measures. Accordingly, the two-component system (TCS) of Streptomyces coelicolor AbrB1/B2, offer amenable ways to study both antibiotic production and resistance. Global transcriptomic comparisons between the wild-type strain S. coelicolor M145 and the mutant Δ abrB , using RNA-Seq, showed that the AbrB1/B2 TCS is implicated in the regulation of different biological processes associated with stress responses, primary and secondary metabolism, and development and differentiation. The Δ abrB mutant showed the up-regulation of antibiotic biosynthetic gene clusters and the down-regulation of the vancomycin resistance gene cluster, according to the phenotypic observations of increased antibiotic production of actinorhodin and undecylprodigiosin, and greater susceptibility to vancomycin. The role of AbrB1/B2 in vancomycin resistance has also been shown by an in silico analysis, which strongly indicates that AbrB1/B2 is a homolog of VraR/S from Staphylococcus aureus and LiaR/S from Enterococcus faecium / Enterococcus faecalis , both of which are implied in vancomycin resistance in these pathogenic organisms that present a serious threat to public health. The results obtained are interesting from a biotechnological perspective since, on one hand, this TCS is a negative regulator of antibiotic production and its high degree of conservation throughout Streptomyces spp. makes it a valuable tool for improving antibiotic production and the discovery of cryptic metabolites with antibiotic action. On the other hand, AbrB1/B2 contributes to vancomycin resistance and is a homolog of VraR/S and LiaR/S, important regulators in clinically relevant antibiotic-resistant bacteria. Therefore, the study of AbrB1/B2 could provide new insight into the mechanism of this type of resistance.

Two-Component Systems of Streptomyces coelicolor: An Intricate Network to Be Unraveled

“…Recent research on TCSs has shown that some are involved in antibiotic resistance such as VanS/R [ 161 ], CsecC/B [ 73 ], and AbrB1/B2 [ 46 ]. This discovery has presented another potential application for this model species, as using the information obtained with their study not only improves the understanding of antibiotic resistance mechanisms in Streptomycetes, but also the highly relevant human pathogens such as S. aureus or E. faecium.…”

“…This system has been described as a negative regulator of antibiotic production (ACT and RED) and a positive regulator of vancomycin resistance [ 46 ].…”

“…This TCS is a homolog of VraR/S ( Staphylococcus aureus ) and LiaR/S ( Enterococcus faecium ), which act as sensors of cell wall damage and are involved in the cell envelope stress response, playing a key role in clinically relevant antibiotic-resistant bacteria [ 46 ].…”

Aplicación de pigmentos producidos por Streptomyces coelicolor en la síntesis de nanopartículas de plata con actividad antimicrobiana

“…El desarrollo e implementación de estrategias contra la propagación de superbacterias es una prioridad para la salud pública. Además de aumentar la conciencia social sobre el uso indiscriminado de antibióticos, enfoques como el descubrimiento de nuevas moléculas con actividad antimicrobiana y el esclarecimiento de los mecanismos de resistencia son medidas comunes que se deben fortalecer (49) .…”

Implicaciones de los sistemas XRE/DUF397 de Streptomyces coelicolor en la producción de antibióticos

“…Dado que el interés en su estudio se debe a su posible implicación en la producción de antibióticos se resalta la información del potencial de las proteínas codificadas por los genes vecinos en la producción de metabolitos secundarios. Por ejemplo, cerca de los genes que codifican el sistema SCO2513/14 están localizado los genes que codifican para un supuesto sistema de dos componentes (SCO2517/18) que regula positivamente la producción de undecilprodigiosina (RED) (Li et al, 2004;Hutchings et al, 2004;Sánchez de la Nieta et al, 2020).…”