Host Stress Signals Stimulate Pneumococcal Transition from Colonization to Dissemination into the Lungs.

Fayez Alghofaili,Hasan Yesilkaya,Bushra Shlla,Morten Danielsen,Vitor E Fernandes,Primrose Freestone,Banaz O Kareem,Julian M Ketley,Hastyar Najmuldeen,Liise-Anne Pirofski

doi:10.1128/mbio.02569-21

Fayez Alghofaili, Hasan Yesilkaya + Show 8 more

Open Access

https://doi.org/10.1128/mbio.02569-21

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Abstract

ABSTRACTStreptococcus pneumoniae is an asymptomatic colonizer of the nasopharynx, but it is also one of the most important bacterial pathogens of humans, causing a wide range of mild to life-threatening diseases. The basis of the pneumococcal transition from a commensal to a parasitic lifestyle is not fully understood. We hypothesize that exposure to host catecholamine stress hormones is important for this transition. In this study, we demonstrated that pneumococci preexposed to a hormone released during stress, norepinephrine (NE), have an increased capacity to translocate from the nasopharynx into the lungs compared to untreated pneumococci. Examination of NE-treated pneumococci revealed major alterations in metabolic profiles, cell associations, capsule synthesis, and cell size. By systemically mutating all 12 two-component and 1 orphan regulatory systems, we also identified a unique genetic regulatory circuit involved in pneumococcal recognition and responsiveness to human stress hormones.

Highlights

Streptococcus pneumoniae is an asymptomatic colonizer of the nasopharynx, but it is one of the most important bacterial pathogens of humans, causing a wide range of mild to life-threatening diseases
We previously demonstrated that S. pneumoniae is stress hormone responsive and that therapeutic levels of norepinephrine both increase pneumococcal growth and alter the expression of genes involved in metabolism and virulence [15]
The bacterial loads in the nasopharyngeal wash samples were the same for mice inoculated with nontreated D39 pneumococci and those inoculated with pneumococci grown in the presence of NE overnight, and no pneumococci were detected in bronchoalveolar lavage (BAL) fluid samples in either the test or control cohorts (Fig. 1A and B)

Summary

Introduction

Streptococcus pneumoniae is an asymptomatic colonizer of the nasopharynx, but it is one of the most important bacterial pathogens of humans, causing a wide range of mild to life-threatening diseases. IMPORTANCE Microbes acquire unique lifestyles under different environmental conditions This is a widespread occurrence, our knowledge of the importance of various host signals and their impact on microbial behavior is not clear despite the therapeutic value of this knowledge. We discovered that catecholamine stress hormones are the host signals that trigger the passage of Streptococcus pneumoniae from a commensal to a parasitic state. ® mbio.asm.org 1 aspects of the shift from colonization to translocation into the lungs are not fully understood, but we believe that host hormonal signals may be involved in this transition. Microbes encounter a variety of chemical signals that can fundamentally affect their behavior, the most studied of which are the catecholamine stress hormones dopamine (Dop), epinephrine (Epi), and norepinephrine (NE) [2]. Given the complex nature of stress hormone-bacterium interactions, it is highly plausible that there are additional unrecognized mechanisms involved in microbial responses to stress hormones

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