In vitro effects of penicillin and telithromycin on the expression of Streptococcus pneumoniae capsule

Brook, Itzhak; Hausfeld, Jeffrey N.

doi:10.1093/jac/dkl261

Cited by 7 publications

(5 citation statements)

References 17 publications

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“…Tateda et al (14) reported that azithromycin (AZM) interferes with autoinducer synthesis of Pseudomonas aeruginosa, leading to a reduction of virulence factor production. Subinhibitory concentrations of telithromycin were shown previously to suppress the capsular formation of Streptococcus pneumoniae (15). On the basis of that previous study, we speculated that macrolides may inhibit the virulence of C. gattii, particularly with respect to reduction of the polysaccharide capsule, and may be responsible for an altered innate immune response, especially that involving neutrophils and macrophages, which is consistent with effective host protection.…”

supporting

confidence: 51%

“…Macrolide exposure significantly reduced the capsule thickness of highly virulent C. gattii, and the amount of CPS was similarly reduced. Previous studies showed that bacteriostatic antibiotics, such as macrolides and clindamycin, reduce capsule size in S. pneumoniae by inhibiting protein synthesis (15). Furthermore, several previous studies demonstrated the effects of inhibiting macrolide-mediated bacterial virulence, especially in P. aeruginosa (11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

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Macrolides Inhibit Capsule Formation of Highly Virulent Cryptococcus gattii and Promote Innate Immune Susceptibility

Nakamura

Ikeda-Dantsuji

Jin

et al. 2019

Antimicrob Agents Chemother

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Cryptococcus gattii is a fungal pathogen, endemic in tropical and subtropical regions, the west coast of Canada, and the United States, that causes a potentially fatal infection in otherwise healthy individuals. Because the cryptococcal polysaccharide capsule is a leading virulence factor due to its resistance against innate immunity, the inhibition of capsule formation may be a promising new therapeutic strategy for C. gattii. Macrolides have numerous nonantibiotic effects, including immunomodulation of mammalian cells and suppression of bacterial (but not fungal) pathogenicity. Thus, we hypothesized that a macrolide would inhibit cryptococcal capsule formation and improve the host immune response. Coincubation with clarithromycin (CAM) and azithromycin significantly reduced the capsule thickness and the amount of capsular polysaccharide of both C. gattii and C. neoformans. CAM-treated C. gattii cells were significantly more susceptible to H 2 O 2 oxidative stress and opsonophagocytic killing by murine neutrophils. In addition, more C. gattii cells were phagocytosed by murine macrophages, resulting in increased production of tumor necrosis factor alpha (TNF-␣) by CAM exposure. After CAM exposure, dephosphorylation of Hog1, one of the mitogen-activated protein kinase (MAPK) signaling pathways of Cryptococcus, was observed in Western blot analysis. In addition, CAM exposure significantly reduced the mRNA expression of LAC1 and LAC2 (such mRNA expression is associated with cell wall integrity and melanin production). These results suggest that CAM may aid in inhibiting capsular formation via the MAPK signaling pathway and by suppressing virulent genes; thus, it may be a useful adjunctive agent for treatment of refractory C. gattii infection.

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supporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Macrolides Inhibit Capsule Formation of Highly Virulent Cryptococcus gattii and Promote Innate Immune Susceptibility

Nakamura

Ikeda-Dantsuji

Jin

et al. 2019

Antimicrob Agents Chemother

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“…Type 1 fimbriae are known to be critical in internalization and IBC formation ( 58 – 60 ); their expression in response to ciprofloxacin and subsequent chronic infection development is likely paramount. Although changes in type 1 fimbria transcript abundance was not observed, posttranscriptional modification or capsule downregulation and enhanced FimH exposure might contribute to the observed changes in antibiotic-induced hemagglutination ( 61 , 62 ). Increased numbers of IBCs are associated with an increased risk of chronic cystitis ( 36 ).…”

Section: Discussionmentioning

confidence: 87%

Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity

Goneau

Hannan

MacPhee

et al. 2015

mBio

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The capacity of subinhibitory levels of antibiotics to modulate bacterial virulence in vitro has recently been brought to light, raising concerns over the appropriateness of low-dose therapies, including antibiotic prophylaxis for recurrent urinary tract infection management. However, the mechanisms involved and their relevance in influencing pathogenesis have not been investigated. We characterized the ability of antibiotics to modulate virulence in the uropathogens Staphylococcus saprophyticus and Escherichia coli. Several antibiotics were able to induce the expression of adhesins critical to urothelial colonization, resulting in increased biofilm formation, colonization of murine bladders and kidneys, and promotion of intracellular niche formation. Mice receiving subinhibitory ciprofloxacin treatment were also more susceptible to severe infections and frequent recurrences. A ciprofloxacin prophylaxis model revealed this strategy to be ineffective in reducing recurrences and worsened infection by creating larger intracellular reservoirs at higher frequencies. Our study indicates that certain agents used for antibiotic prophylaxis have the potential to complicate infections.

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“…20 For example, antibiotics acting on bacterial cell walls can inhibit the synthesis of capsular polysaccharides in Streptococcus pneumoniae. 21 In the study by Nomura et al, it was found that after the treatment of K. pneumoniae with different drugs in 1/4MIC, penicillins, cephalosporins and monoamides could significantly reduce the capsular thickness, quinolones had little effect on the capsular thickness, while aminoglycosides, macrolides and carbapenems showed no significant change in the capsular thickness. 22 Since the mid-1980s, hvKp, which is usually presented as an HMV phenotype, has become a clinically important pathogen and often causes severe disseminated infections.…”

Section: Discussionmentioning

confidence: 98%

The Anti-Virulence Effect of Sub-Minimal Inhibitory Concentrations of Levofloxacin on Hypervirulent Klebsiella pneumoniae

Ma¹,

Zhang²,

Yue³

et al. 2022

IDR

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Background: Hypervirulent Klebsiella pneumoniae (hvKp) is best described as a virulent pathogen and generally associated with the hypermucoviscosity phenotype. Increased capsule and aerobactin production are established important hvKp-specific virulence factors. Although hvKp strains have been relatively susceptible to antimicrobials, given the high morbidity and mortality, there is a critical need for alternative strategies for the treatment of hvKp infections. Thus, the anti-virulence therapy has been targeted for the hvKp development of therapeutics. Materials and Methods: Four hvKp isolates with hypermucoviscous phenotype were used in our experiments. Mucoviscosity of the capsule can be assessed by low-speed centrifugation of cultures. CPS amount was determined by glucuronic acid content. The capsule thickness was measured under microscope after ink staining. The transcriptions of gene were measured by quantitative real-time PCR (qRT-PCR). The effect of levofloxacin on the resistance of K. pneumoniae to phagocytosis by macrophages and mouse lethality assay was observed. Results: Our data revealed that sub-Minimal Inhibitory Concentrations (sub-MIC) of LVX reduce mucoviscosity and CPS production of hvKp. Microscopic observations demonstrated that the capsule of hvkp bacteria became thinned after treatment with LVX. qRT-PCR showed decreased transcript levels of rmpA, wzi, magA, iroN and icuA genes. Down-regulation of these virulence genes occurred leading to increased susceptibility to phagocytosis by macrophages. Mouse lethality assay revealed that the wild strain had the LD50 of 10 3 CFU, while the sub-MIC LVX-treated bacteria had the LD50 of 10 5 CFU. Conclusion:Our data suggested that LVX may serve as a potential anti-virulence agent for refractory infection by hvKp.

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In vitro effects of penicillin and telithromycin on the expression of Streptococcus pneumoniae capsule

Cited by 7 publications

References 17 publications

Macrolides Inhibit Capsule Formation of Highly Virulent Cryptococcus gattii and Promote Innate Immune Susceptibility

Macrolides Inhibit Capsule Formation of Highly Virulent Cryptococcus gattii and Promote Innate Immune Susceptibility

Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity

The Anti-Virulence Effect of Sub-Minimal Inhibitory Concentrations of Levofloxacin on Hypervirulent Klebsiella pneumoniae

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