Transcriptome analysis of the responses of Staphylococcus aureus to antimicrobial peptides and characterization of the roles of vraDE and vraSR in antimicrobial resistance

<p>Abstract</p> <p>Background</p> <p>Understanding how pathogens respond to antimicrobial peptides, and how this compares to currently available antibiotics, is crucial for optimizing antimicrobial therapy. <it>Staphylococcus aureus </it>has several known resistance mechanisms against human cationic antimicrobial peptides (CAMPs). Gene expression changes in <it>S. aureus </it>strain Newman exposed to linear CAMPs were analyzed by DNA microarray. Three antimicrobial peptides were used in the analysis, two are derived from frog, temporin L and dermaseptin K4-S4(1-16), and the ovispirin-1 is obtained from sheep.</p> <p>Results</p> <p>The peptides induced the VraSR cell-wall regulon and several other genes that are also up-regulated in cells treated with vancomycin and other cell wall-active antibiotics. In addition to this similarity, three genes/operons were particularly strongly induced by the peptides: <it>vraDE</it>, SA0205 and SAS016, encoding an ABC transporter, a putative membrane-bound lysostaphin-like peptidase and a small functionally unknown protein, respectively. Ovispirin-1 and dermaseptin K4-S4(1-16), which disrupt lipid bilayers by the carpet mechanism, appeared to be strong inducers of the <it>vraDE </it>operon. We show that high level induction by ovispirin-1 is dependent on the amide modification of the peptide C-terminus. This suggests that the amide group has a crucial role in the activation of the Aps (GraRS) sensory system, the regulator of <it>vraDE</it>. In contrast, temporin L, which disrupts lipid bilayers by forming pores, revealed a weaker inducer of <it>vraDE </it>despite the C-terminal amide modification. Sensitivity testing with CAMPs and other antimicrobials suggested that VraDE is a transporter dedicated to resist bacitracin. We also showed that SA0205 belongs to the VraSR regulon. Furthermore, VraSR was shown to be important for resistance against a wide range of cell wall-active antibiotics and other antimicrobial agents including the amide-modified ovispirin-1, bacitracin, teicoplanin, cefotaxime and 10 other β-lactam antibiotics, chlorpromazine, thioridazine and EGTA.</p> <p>Conclusion</p> <p>Defense against different CAMPs involves not only general signaling pathways but also CAMP-specific ones. These results suggest that CAMPs or a mixture of CAMPs could constitute a potential additive to standard antibiotic treatment.</p

Genetic evolution of invasive emm28 Streptococcus pyogenes strains and significant association with puerperal infections in young women in Finland

Objectives: Streptococcus pyogenes or group A streptococcus (GAS) is a human specific pathogen that annually infects over 700 million individuals. GAS strains of type emm28 are an abundant cause of invasive infections in Europe and North America.Methods: We conducted a population-based study on bacteraemic emm28 GAS cases in Finland, from 1995 to 2015. Whole-genome sequencing (WGS) was used to genetically characterize the bacterial isolates. Bayesian analysis of the population structure was used to define genetic clades. Register-linkage analysis was performed to test for association of emm28 GAS with delivery- or postpartum-related infections. A genome-wide association study was used to search for DNA sequences associated with delivery or puerperal infections.Results: Among 3060 bacteraemic cases reported during the study period, 714 were caused by emm28. Women comprised a majority of cases (59 %, 422/714), and were significantly over-represented (84.4 %, 162/192, p Conclusions: Women of childbearing age were significantly overrepresented among bacteraemic emm28 GAS cases, and in particular were strongly associated with delivery and puerperium cases over the 21 years studied. The molecular mechanisms behind these associations are unclear and warrant further investigation.</p

Bakteerien mikrobilääkeherkkyyden tuloksen tulkinta muuttuu

Bakteerien mikrobilääkeherkkyysmäärityksissä herkän (S) ja resistentin (R) tuloksen määritelmät pysyvät ennallaan, mutta välimuotoisesti herkän (I) tuloksen tulkinta on muuttumassa. Jatkossa I-tulos tarkoittaa sitä, että bakteerin aiheuttama infektio on hoidettavissa kyseisellä lääkkeellä, mutta annostuksen on oltava riittävän suuri. Suomessa uusi määritelmä otetaan käyttöön asteittain vuoden 2021 aikana

Bakteerien mikrobilääkeresistenssi Suomessa : Finres 2020

Vuosittainen Finres-raportti kuvaa kattavasti Suomen resistenssitilannetta ja sen kehittymistä viimeisen kymmenenvuoden ajalta. Raportissa on koottu yhteen kliinisten mikrobiologianlaboratorioiden ja THL:n Mykobakteerilaboratorion vuosittain rutiinisti tuottamaa mikrobilääkeherkkyystietoa. Finres-raportin resistenssiseurantatiedot koostuvat pääosin kliinisistä infektioista eristettyjen bakteerien resistenssitiedoista

Bakteerien mikrobilääkeherkkyyden tuloksen tulkinta muuttuu

Bakteerien mikrobilääkeherkkyysmäärityksissä herkän (S) ja resistentin (R) tuloksen määritelmät pysyvät ennallaan, mutta välimuotoisesti herkän (I) tuloksen tulkinta on muuttumassa. Jatkossa I-tulos tarkoittaa sitä, että bakteerin aiheuttama infektio on hoidettavissa kyseisellä lääkkeellä, mutta annostuksen on oltava riittävän suuri. Suomessa uusi määritelmä otetaan käyttöön asteittain vuoden 2021 aikana.publishedVersio