Crystal Structure of Mannose Specific IIA Subunit of Phosphotransferase System from Streptococcus pneumoniae.

Malgorzata Magoch,Bozena Boczkus,Pikyee Ma,Ana Rute Neves,Przemyslaw Nogly,Przemyslaw Grudnik,Grzegorz Dubin,Margarida Archer

doi:10.3390/molecules25204633

Abstract

Streptococcus pneumoniae is a frequent bacterial pathogen of the human respiratory tract causing pneumonia, meningitis and sepsis, a serious healthcare burden in all age groups. S. pneumoniae lacks complete respiratory chain and relies on carbohydrate fermentation for energy generation. One of the essential components for this includes the mannose phosphotransferase system (Man-PTS), which plays a central role in glucose transport and exhibits a broad specificity for a range of hexoses. Importantly, Man-PTS is involved in the global regulation of gene expression for virulence determinants. We herein report the three-dimensional structure of the EIIA domain of S. pneumoniae mannose phosphotransferase system (SpEIIA-Man). Our structure shows a dimeric arrangement of EIIA and reveals a detailed molecular description of the active site. Since PTS transporters are exclusively present in microbes and sugar transporters have already been suggested as valid targets for antistreptococcal antibiotics, our work sets foundation for the future development of antimicrobial strategies against Streptococcus pneumoniae.

Highlights

Streptococcus pneumoniae, a natural inhabitant of human nasopharynx, is capable of progressing to sterile sites in the human body, causing serious diseases including pneumonia, meningitis and sepsis [1]
By further exploring the structural analogies resembled in SpEIIA-Man, with only a single sidechain substitution at positon 24 where isoluecine is here we propose the following sequence of events: the SpEIIA-Man surface that interacts with Hpr found in place of leucine
By further exploring the structural analogies here we propose the following originates from both monomers and encompasses the area around the essential sequence of events: the SpEIIA-Man surface that interacts with Hpr originates from both monomers and encompasses the area around the essential His10 of subunit A where the surface exhibits a shallow groove, complement to convex surface of Hpr

Summary

Introduction

Streptococcus pneumoniae, a natural inhabitant of human nasopharynx, is capable of progressing to sterile sites in the human body, causing serious diseases including pneumonia, meningitis and sepsis [1]. S. pneumoniae accounts for more deaths than any other bacterium [2]. According to the World Health Organization (WHO), streptococcal infections are responsible for about 1 million deaths per year in children under 5 years of age. High rate of resistance acquisition to traditional antibiotics and the re-emergence of non-vaccine type strains forebode increasing healthcare threat in the forthcoming years. The development of new therapeutic and preventive strategies is required, which calls for better understanding of streptococcal pathogenesis.

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Conclusion