Evaluating the Interplay Between Biofilm Formation and Antibiotic Resistance in Klebsiella pneumoniae

Sammanfattning

Antibiotic resistance is an increasing problem worldwide and without new antibiotics, or ways to prevent and inhibit resistance, people will die from diseases that have previously been treatable. A species known for increasingly gaining antibiotic resistance is Klebsiella pneumoniae, having resistance genes found in both plasmids and chromosomes. K. pneumoniae can not only live planktonically but also in bacterial communities attached to each other and possibly also a surface, called biofilms. This way of growth makes it harder for some antibiotic drugs to reach targets further down in the biofilm where metabolic activity is lower. To increase resistance, bacteria can also produce enzymes like β-lactamases that break down the structure of β-lactam antibiotics such as penicillin, cephalosporins, carbapenems and monobactams. In this thesis we aim to clarify how β-lactamase producers like K. pneumoniae form and behave in biofilms as well as study how this relates to antibiotic resistance. We do this by inserting plasmids encoding β-lactamase genes in different strains and observing their growth in planktonic and biofilm states, as well as evaluating how K. pneumoniae is affected by β-lactam antibiotics. The results showed that the β-lactamase gene CTX-M-15 was associated with the highest fitness cost. However, there was no indication that β-lactamase producers in general were worse biofilm producers, which previous research has suggested. Out of the tested strains, one of the strains with a mutation in a type 3 fimbriae gene (DA58322, mrkD mutant) was the most affected by both antibiotics when growing in biofilms and by carrying the pBAD18 plasmid including genes, both in biofilm and planktonic. More research needs to be done in the field to study the effect of antibiotic treatment on biofilms, as well as investigate ways to inhibit the activity of β-lactamases to reduce antibiotic resistance.