Discovery of Brominated Alboflavusins With Anti-MRSA Activities.

Chao Li,Haoyue Zhang,Zhitang Lyu,Yihua Chen,Zhengyan Guo,Wuyundalai Bao

doi:10.3389/fmicb.2021.641025

Abstract

As methicillin-resistant Staphylococcus aureus (MRSA) is becoming a serious pathogenic threaten to human health worldwide, there is an urgent need to discover new antibiotics for the treatment of MRSA infections. Alboflavusins (AFNs) are a group of halogenated cyclohexapeptides with anti-MRSA activities. In this study, two novel brominated AFN congeners (compounds 1 and 2) were isolated from the wild-type strain Streptomyces alboflavus sp. 313 that was fermented in the production medium supplemented with NaBr; two new (compounds 3 and 5) and a known (compound 4) dehelogenated AFN congeners were isolated from S. alboflavus ΔafnX, in which the tryptophan halogenase gene afnX was inactivated. The structures of these compounds were assigned by careful NMR and MS analyses. The anti-MRSA activities of varied AFN congeners were assessed against different MRSA strains, which revealed that compounds 1 and 2 with bromine displayed effective activities against the tested MRSA strains. Especially, compound 2 showed good anti-MRSA activity, while compounds 3, 4, and 5 without halogen exhibited weak anti-MRSA activities, outlining the influence of halogen substitution to the bioactivities of AFNs.

Highlights

Staphylococcus aureus (SA) has become a serious pathogenic threat to human health worldwide (Tong et al, 2015; Lee et al, 2018)
According to the similarity of UV adsorption and the isotope abundance peaks (Figure 1), two major AFN congeners (1 and 2) containing one bromine atom were discovered from S. alboflavus sp. 313, while three AFN congeners without chlorine (3, 4, and 5) were detected in the crude extract of S. alboflavus afnX
30 L fermentation broths of S. alboflavus sp. 313 and the afnX mutant were collected for compound isolation and 10.2 mg 1, 6.7 mg 2, 3.4 mg 3, 5.6 mg 4, and 4.2 mg 5 were obtained for structure elucidation

Summary

Introduction

Staphylococcus aureus (SA) has become a serious pathogenic threat to human health worldwide (Tong et al, 2015; Lee et al, 2018). It usually causes superficial skin and soft tissue infections, sometimes even leading to fatal blood infections and pneumonia (Bhattacharya et al, 2015; Water et al, 2015). In the latest global assessment of antibiotic resistance, SA is considered to be a high priority pathogen (Tacconelli et al, 2018). Methicillin-resistant SA (MRSA) showed the higher pathogenicity, infection rate and mortality rate (Cosgrove et al, 2003; Stefani et al, 2012). Antibiotic therapy has been considered the primary treatment strategy for SA infection (Bal et al, 2017), and its widespread application has greatly improved the prognosis of patients with SA

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Conclusion