Streptococcus pneumoniae Senses a Human-like Sialic Acid Profile via the Response Regulator CiaR

Hentrich, Karina; Löfling, Jonas; Pathak, Anuj; Nizet, Victor; Varki, Ajit; Henriques‐Normark, Birgitta

doi:10.1016/j.chom.2016.07.019

Cited by 44 publications

(36 citation statements)

References 65 publications

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“…The presence of various amounts of sialidase-resistant Sias may therefore contribute to selection of influenza virus populations with HA variants, while its display on some horse and guinea pig cells in culture may provide an in vitro system suitable for the study of this modified Sia and its interactions with influenza and other viruses. Little is known about the direct effects of 4-O-Ac Sia on other microbes and pathogens, but their effects on sialidase (neuramindase) function would likely alter susceptibility in many respiratory viral and bacterial pathogens ( 66 – 68 ).…”

Section: Discussionmentioning

confidence: 99%

Distribution of O-Acetylated Sialic Acids among Target Host Tissues for Influenza Virus

Wasik

Barnard

Ossiboff

et al. 2017

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Sialic acids (Sias) are key glycans that control or modulate many normal cell and tissue functions while also interacting with a variety of pathogens, including many different viruses. Sias are naturally displayed in a variety of different forms, with modifications at several positions that can alter their functional interactions with pathogens. In addition, Sias are often modified or removed by enzymes such as host or pathogen esterases or sialidases (neuraminidases), and Sia modifications can alter those enzymatic activities to impact pathogen infections. Sia chemical diversity in different hosts and tissues likely alters the pathogen-host interactions and influences the outcome of infection. Here we explored the display of 4-O-acetyl, 9-O-acetyl, and 7,9-O-acetyl modified Sia forms in some target tissues for influenza virus infection in mice, humans, birds, guinea pigs, ferrets, swine, horses, and dogs, which encompass many natural and laboratory hosts of those viruses.

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Section: Discussionmentioning

confidence: 99%

Distribution of O-Acetylated Sialic Acids among Target Host Tissues for Influenza Virus

Wasik

Barnard

Ossiboff

et al. 2017

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“…Sialic acid released by NanA has been shown to act as a signal, increasing bacterial loads in the nasopharynx of mice colonized with S. pneumoniae and facilitating invasion of nasal tissue and progression to pneumonia and meningitis 105,106 . Such signalling involves the two- transcriptional regulatory protein CiaR and requires sialic acid uptake by the transporter SatABC, and this results in increased pneumococcal resistance to antimicrobial reactive oxygen species 107 . NanA can also trigger TGFβ signalling pathways, leading to endothelial cell invasion 108 .…”

Section: Invasive Pneumococcal Diseasementioning

confidence: 99%

Streptococcus pneumoniae: transmission, colonization and invasion

2018

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Streptococcus pneumoniae as a complex relationship with its obligate human host. On the one hand, the pneumococci are highly adapted commensals, and their main reservoir on the mucosal surface of the upper airways of carriers enables transmission. On the other hand, they can cause severe disease when bacterial and host factors allow them to invade essentially sterile sites, such as the middle ear spaces, lungs, bloodstream and meninges. Transmission, colonization and invasion depend on the remarkable ability of S. pneumoniae to evade or take advantage of the host inflammatory and immune responses. The different stages of pneumococcal carriage and disease have been investigated in detail in animal models and, more recently, in experimental human infection. Furthermore, widespread vaccination and the resulting immune pressure have shed light on pneumococcal population dynamics and pathogenesis. Here, we review the mechanistic insights provided by these studies on the multiple and varied interactions of the pneumococcus and its host.

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“…The milder phenotype of the hk11 H184A strain than that of rr11 D53A suggested that RR11 is phosphorylated by an alternative phosphoryl group donor(s) besides HK11. Hentrich et al reported that intracellular acetyl phosphate generated by pyruvate kinase SpxB is capable of phosphorylating the RR05 (CiaR) response regulator [50]. To elaborate on the function of HK11 in phase variation, we constructed a "hyper-active" mutant of HK11 by making a T-to-P mutation in the 190 th threonine residue.…”

Section: Phosphorylated Form Of Rr11 Drives Pneumococci Toward the Omentioning

confidence: 99%

Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems

Wang

et al. 2020

PLoS Pathog

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Streptococcus pneumoniae is well known for phase variation between opaque (O) and transparent (T) colonies within clonal populations. While the O variant is specialized in invasive infection (with a thicker capsule and higher resistance to host clearance), the T counterpart possesses a relatively thinner capsule and thereby higher airway adherence and colonization. Our previous study found that phase variation is caused by reversible switches of the "opaque ON-or-OFF" methylomes or methylation patterns of pneumococcal genome, which is dominantly driven by the PsrA-catalyzed inversions of the DNA methyltransferase hsdS genes. This study revealed that switch frequency between the O and T variants is regulated by five transcriptional response regulators (rr) of the two-component systems (TCSs). The mutants of rr06, rr08, rr09, rr11 and rr14 produced significantly fewer O and more T colonies. Further mutagenesis revealed that RR06, RR08, RR09 and RR11 enrich the O variant by modulating the directions of the PsrA-catalyzed inversion reactions. In contrast, the impact of RR14 (RitR) on phase variation is independent of PsrA. Consistently, SMRT sequencing uncovered significantly diminished "opaque ON" methylome in the mutants of rr06, rr08, rr09 and rr11 but not that of rr14. Lastly, the phosphorylated form of RR11 was shown to activate the transcription of comW and two sugar utilization systems that are necessary for maintenance of the "opaque ON" genotype and phenotype. This work has thus uncovered multiple novel mechanisms that balance pneumococcal epigenetic status and physiology.

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Streptococcus pneumoniae Senses a Human-like Sialic Acid Profile via the Response Regulator CiaR

Cited by 44 publications

References 65 publications

Distribution of O-Acetylated Sialic Acids among Target Host Tissues for Influenza Virus

Distribution of O-Acetylated Sialic Acids among Target Host Tissues for Influenza Virus

Streptococcus pneumoniae: transmission, colonization and invasion

Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems

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