1. Главная
  2. Ресурсы
  3. Библиотечный поиск
A Low-AffinityPenicillin-BindingProtein 2x Variant IsRequired forHeteroresistance inStreptococcuspneumoniae Hansjürg EngelMoana MikaDalia Denapaite2014 год

A Low-Affinity Penicillin-Binding Protein 2x Variant Is Required for Heteroresistance in Streptococcus pneumoniae
статья из журнала

Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: ABSTRACT Heteroresistance to penicillin in Streptococcus pneumoniae is the ability of subpopulations to grow at a higher antibiotic concentration than expected from the MIC. This may render conventional resistance testing unreliable and lead to therapeutic failure. We investigated the role of the primary β-lactam resistance determinants, penicillin-binding protein 2b (PBP2b) and PBP2x, and the secondary resistance determinant PBP1a in heteroresistance to penicillin. Transformants containing PBP genes from the heteroresistant strain Spain 23F 2349 in the nonheteroresistant strain R6 background were tested for heteroresistance by population analysis profiling (PAP). We found that pbp2x , but not pbp2b or pbp1a alone, conferred heteroresistance to R6. However, a change of pbp2x expression was not observed, and therefore, expression does not correlate with an increased proportion of resistant subpopulations. In addition, the influence of the CiaRH system, mediating PBP-independent β-lactam resistance, was assessed by PAP on ciaR disruption mutants but revealed no heteroresistant phenotype. We also showed that the highly resistant subpopulations (HOM*) of transformants containing low-affinity pbp2x undergo an increase in resistance upon selection on penicillin plates that partially reverts after passaging on selection-free medium. Shotgun proteomic analysis showed an upregulation of phosphate ABC transporter subunit proteins encoded by pstS , phoU , pstB , and pstC in these highly resistant subpopulations. In conclusion, the presence of low-affinity pbp2x enables certain pneumococcal colonies to survive in the presence of β-lactams. Upregulation of phosphate ABC transporter genes may represent a reversible adaptation to antibiotic stress.
Год издания: 2014
Авторы: Hansjürg Engel, Moana Mika, Dalia Denapaite, Regine Hakenbeck, Kathrin Mühlemann, Manfred Heller, Lucy J. Hathaway, Markus Hilty
Издательство: American Society for Microbiology
Источник: Antimicrobial Agents and Chemotherapy
Ключевые слова: Pneumonia and Respiratory Infections, Antibiotic Resistance in Bacteria, Pneumocystis jirovecii pneumonia detection and treatment
Другие ссылки: Antimicrobial Agents and Chemotherapy (PDF)
Antimicrobial Agents and Chemotherapy (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)