Search

ABSTRACT The overuse of antibiotics in humans and livestock has driven the emergence and spread of antimicrobial resistance and has therefore prompted research on the discovery of novel antibiotics. Complestatin (Cm) and corbomycin (Cb) are glycopeptide antibiotics with an unprecedented mechanism of action that is active even against methicillin-resistant and daptomycin-resistant Staphylococcus aureus. They bind to peptidoglycan and block the activity of peptidoglycan hydrolases required for remodeling the cell wall during growth. Bacterial signaling through two-component transduction systems (TCSs) has been associated with the development of S. aureus antimicrobial resistance. However, the role of TCSs in S. aureus susceptibility to Cm and Cb has not been previously addressed. In this study, we determined that, among all 16 S. aureus TCSs, VraSR is the only one controlling the susceptibility to Cm and Cb. Deletion of vraSR increased bacterial susceptibility to both antibiotics. Epistasis analysis with members of the vraSR regulon revealed that deletion of spdC, which encodes a membrane protein that scaffolds SagB for cleavage of peptidoglycan strands to achieve physiological length, in the vraSR mutant restored Cm and Cb susceptibility to wild-type levels. Moreover, deletion of either spdC or sagB in the wild-type strain increased resistance to both antibiotics. Further analyses revealed a significant rise in the relative amount of peptidoglycan and its total degree of cross-linkage in ΔspdC and ΔsagB mutants compared to the wild-type strain, suggesting that these changes in the cell wall provide resistance to the damaging effect of Cm and Cb. IMPORTANCE Although Staphylococcus aureus is a common colonizer of the skin and digestive tract of humans and many animals, it is also a versatile pathogen responsible for causing a wide variety and number of infections. Treatment of these infections requires the bacteria to be constantly exposed to antibiotic treatment, which facilitates the selection of antibiotic-resistant strains. The development of new antibiotics is, therefore, urgently needed. In this paper, we investigated the role of the sensory system of S. aureus in susceptibility to two new antibiotics: corbomycin and complestatin. The results shed light on the cell-wall synthesis processes that are affected by the presence of the antibiotic and the sensory system responsible for coordinating their activity.

Introduction: Humanity has benefited from the presence of antibiotics to treat bacterial infections for decades. However, due to the overuse of antibiotics bacteria develop resistance against these drugs, leading to the emergence of untreatable superbugs. Antibiotic resistance is one of the biggest threats to global health. It is rising to dangerously high levels with hundreds of thousands of deaths reported worldwide every year. Dealing with the ongoing antibiotic crisis requires the discovery of compounds with novel mechanisms of action that are capable to treat drug-resistant infections. A newly found antibiotic from a glycopeptides family with “a unique approach” to attacking and killing bacteria was announced in 2020. The purpose of our work is to provide information about Corbomycin. Materials and methods: a review of scientific literature and studies that provide information on Corbomycin. Conclusion: In recent years, researchers have been increasingly searching for new approaches to treat life-threatening bacterial infections. Corbomycin – an antibiotic that kills bacteria by blocking the function of their cell wall is a promising clinical candidate in the fight against antimicrobial resistance.

Introduction: Humanity has benefited from the presence of antibiotics to treat bacterial infections for decades. However, due to the overuse of antibiotics bacteria develop resistance against these drugs, leading to the emergence of untreatable superbugs. Antibiotic resistance is one of the biggest threats to global health. It is rising to dangerously high levels with hundreds of thousands of deaths reported worldwide every year. Dealing with the ongoing antibiotic crisis requires the discovery of compounds with novel mechanisms of action that are capable to treat drug-resistant infections. A newly found antibiotic from a glycopeptides family with "a unique approach" to attacking and killing bacteria was announced in 2020. The purpose of our work is to provide information about Corbomycin. Materials and methods: a review of scientific literature and studies that provide information on Corbomycin. Conclusion: In recent years, researchers have been increasingly searching for new approaches to treat life-threatening bacterial infections. Corbomycin - an antibiotic that kills bacteria by blocking the function of their cell wall is a promising clinical candidate in the fight against antimicrobial resistance. [ABSTRACT FROM AUTHOR]

The overuse of antibiotics in humans and livestock has driven the emergence and spread of antimicrobial resistance and has therefore prompted research on the discovery of novel antibiotics. Complestatin (Cm) and corbomycin (Cb) are glycopeptide antibiotics with an unprecedented mechanism of action that is active even against methicillin-resistant and daptomycin-resistant Staphylococcus aureus . They bind to peptidoglycan and block the activity of peptidoglycan hydrolases required for remodeling the cell wall during growth. Bacterial signaling through two-component transduction systems (TCSs) has been associated with the development of S. aureus antimicrobial resistance. However, the role of TCSs in S. aureus susceptibility to Cm and Cb has not been previously addressed. In this study, we determined that, among all 16 S. aureus TCSs, VraSR is the only one controlling the susceptibility to Cm and Cb. Deletion of vraSR increased bacterial susceptibility to both antibiotics. Epistasis analysis with members of the vraSR regulon revealed that deletion of spdC, which encodes a membrane protein that scaffolds SagB for cleavage of peptidoglycan strands to achieve physiological length, in the vraSR mutant restored Cm and Cb susceptibility to wild-type levels. Moreover, deletion of either spdC or sagB in the wild-type strain increased resistance to both antibiotics. Further analyses revealed a significant rise in the relative amount of peptidoglycan and its total degree of cross-linkage in ΔspdC and ΔsagB mutants compared to the wild-type strain, suggesting that these changes in the cell wall provide resistance to the damaging effect of Cm and Cb. IMPORTANCE Although Staphylococcus aureus is a common colonizer of the skin and digestive tract of humans and many animals, it is also a versatile pathogen responsible for causing a wide variety and number of infections. Treatment of these infections requires the bacteria to be constantly exposed to antibiotic treatment, which facilitates the selection of antibiotic-resistant strains. The development of new antibiotics is, therefore, urgently needed. In this paper, we investigated the role of the sensory system of S. aureus in susceptibility to two new antibiotics: corbomycin and complestatin. The results shed light on the cell-wall synthesis processes that are affected by the presence of the antibiotic and the sensory system responsible for coordinating their activity.