Dissection of novel resistance mechanisms in Cupriavidus metallidurans

Ali Md Muntasir

Promoter

Charlier Daniel, (VUB), dcharlie@vub.ac.be

SCK•CEN Mentor

Van Houdt Rob
rob.van.houdt@sckcen.be
+32 14 33 27 28

Expert group

Microbiology

PhD started

2015-10-01

Short project description

Cupriavidus metallidurans strains, which belong to the Burkholderiacea family and are characterized by multiple metal resistances, have been mostly isolated from industrial sites linked to mining, metallurgic and chemical industries. These strains are often typified by their large arsenal of mobile genetic elements (plasmids, transposons, genomic islands) that carry determinants allowing the strains to specifically adapt to their environment. For example, C. metallidurans type strain CH34 carries many determinants for metal resistance on its megaplasmids pMOL28 and pMOL30. Interestingly, while they often thrive in oligotrophic niches like industrial sites but also water systems (such as drinking water systems and even spent nuclear fuel pools), Cupriavidus isolates are increasingly being recovered from medically-relevant sources.

Studies at SCK•CEN underscored the rapid evolution of C. metallidurans strains towards significantly increased metal resistance. Surprisingly, the canonical mechanisms did not participate in this adaptive evolution. In contrast, a novel and unique resistance mechanism, involving an uncharacterized small periplasmic protein, was discovered. This small protein belongs to a group of ca. 20 homologous proteins distributed over the C. metallidurans genome. Other members of this group are transcriptionally induced by different metals or other stressors like oxidative stress and ionizing radiation, suggesting they may participate in specific stress response strategies of the cell.

Objective

In essence, this project aims to dissect the genetic regulation, molecular characteristics and physiological impact of these novel small periplasmic proteins, with regard to their role in the response to stress (e.g. metals). These objectives will be met by studying their phenotypic impact in C. metallidurans with regard to resistance, and by dissecting the genetic regulation of their encoding genes. The findings of this project will provide insights in (i) the functionality of a novel protein family, (ii) an unanticipated mechanism of resistance and (iii) the adaptive potential of C. metallidurans strains.