Commensal Streptococcus mitis is a unique vector for oral mucosal vaccination

Streptococcus mitis-oralis (S. mitis-oralis) infections are increasingly prevalent in specific populations, including neutropenic cancer and endocarditis patients. S. mitis-oralis strains have a propensity to evolve rapid, high-level and durable resistance to daptomycin (DAP-R) in vitro and in vivo, although the mechanism(s) involved remain incompletely defined. We examined mechanisms of DAP-R versus cross-resistance to cationic host defense peptides (HDPs), using an isogenic S. mitis-oralis strain-pair: (i) DAP-susceptible (DAP-S) parental 351-WT (DAP MIC = 0.5 µg/mL), and its (ii) DAP-R variant 351-D10 (DAP MIC > 256 µg/mL). DAP binding was quantified by flow cytometry, in-parallel with temporal (1–4 h) killing by either DAP or comparative prototypic cationic HDPs (hNP-1; LL-37). Multicolor flow cytometry was used to determine kinetic cell responses associated with resistance or susceptibility to these molecules. While overall DAP binding was similar between strains, a significant subpopulation of 351-D10 cells hyper-accumulated DAP (>2–4-fold vs. 351-WT). Further, both DAP and hNP-1 induced cell membrane (CM) hyper-polarization in 351-WT, corresponding to significantly greater temporal DAP-killing (vs. 351-D10). No strain-specific differences in CM permeabilization, lipid turnover or regulated cell death were observed post-exposure to DAP, hNP-1 or LL-37. Thus, the adaptive energetics of the CM appear coupled to the outcomes of interactions of S. mitis-oralis with DAP and selected HDPs. In contrast, altered CM permeabilization, proposed as a major mechanism of action of both DAP and HDPs, did not differentiate DAP-S vs. DAP-R phenotypes in this S. mitis-oralis strain-pair.

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Streptococcus infantis, Streptococcus mitis, and Streptococcus oralis Strains With Highly Similar cps5 Loci and Antigenic Relatedness to Serotype 5 Pneumococci

Frontiers in Microbiology ◽

10.3389/fmicb.2018.03199 ◽

2019 ◽

Vol 9 ◽

Cited By ~ 22

Author(s):

Fabiana Pimenta ◽

Robert E. Gertz ◽

So Hee Park ◽

Ellie Kim ◽

Iaci Moura ◽

...

Keyword(s):

Streptococcus Mitis ◽

Streptococcus Oralis ◽

Antigenic Relatedness ◽

Serotype 5

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Inhibition of microbial adherence by sphinganine

Canadian Journal of Microbiology ◽

10.1139/m92-158 ◽

1992 ◽

Vol 38 (9) ◽

pp. 983-985 ◽

Cited By ~ 22

Author(s):

Debra Jan Bibel ◽

Raza Aly ◽

Henry R. Shinefield

Keyword(s):

Staphylococcus Aureus ◽

Infectious Diseases ◽

Therapeutic Agents ◽

Eukaryotic Cells ◽

Buccal Cells ◽

Streptococcus Mitis ◽

Buccal Epithelial Cells ◽

Mucosal Cells ◽

Microbial Adherence ◽

Complex Sphingolipids

Sphingosines (precursors and degeneration products of complex sphingolipids) are mediators in membrane second-messenger cascades and in a wide variety of functions in eukaryotic cells. Sphingosines are also lethal for gram-positive microorganisms. In addition to its direct effect, sphinganine is here reported to affect the adherence of Streptococcus mitis to buccal epithelial cells and of Staphylococcus aureus to nasal mucosal cells after incubation for 90 min at 37 °C. When the bacteria were pretreated with 8.1, 16.2, 32.5, or (for Strep. mitis) 65 μM sphinganine for 60 min at 37 °C, adherence counts were reduced for Staph. aureus by 27, 37, and 60% and for Strep. mitis by 19, 44, 54, and 73%, respectively (p < 0.001). In contrast, pretreatment of buccal cells with 81.2 μM lipid increased adherence by 14% (p < 0.01), but no change occurred at either 16.2 or 325 μM lipid. These results further demonstrate the double-edged ability of sphingosines to regulate cellular activities and their potential as multifunctional therapeutic agents for infectious diseases. Key words: adherence, sphingosine, Staphylococcus aureus, Streptococcus mitis.

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