Ph.D. Defense by Katharina Vester Opstrup

Ph.D. Defense by Katharina Vester Opstrup

Katharina Vester Opstrup will defend her Ph.D. thesis "Serum and antibiotic resistance of Klebsiella pneumoniae blood isolates"

Time

28.01.2022 kl. 13.00 - 16.00

Description

PROGRAM

13.00 Opening by the Moderator Svend Birkelund
13.05 PhD lecture by Katharina Vester Opstrup
13.50 Break
14.00 Questions and comments from the Committee
          Questions and comments from the audience at the Moderator’s discretion
16.00 Conclusion of the session by the Moderator


EVALUATION COMITEE

The Faculty Council has appointed the following adjudication committee to evaluate the thesis and the associated lecture: 

Dr. Jens Kjølseth Møller, Klinisk Mikrobiologi, Vejle Hospital

Dr. Sebastian Albertí, Health Sciences, University of the Balearic Islands

 

Chairman:

Dr. Owe Wiborg, Aalborg Universitet

Moderator:

Dr. Svend Birkelund, Aalborg Universitet

 

ABSTRACT

Acting as primarily an opportunistic pathogen, the gram-negative encapsulated bacterium Klebsiella pneumoniae causes severe infections such as sepsis, bacteremia and pneumonia. Due to an alarming increase in blood stream infections caused by K. pneumoniae reliable and efficient treatment is warranted. However, recent years have proven this stealth pathogen to be a fundamental trafficker of antibiotic resistance genes. One of the first challenges to overcome for an intruding pathogen when entering the host is the complement system, a key player of the innate immune system in the defense against bacterial infections. Discovering interactions between complement and K. pneumoniae can provide important knowledge useful in treating multi-drug resistant K. pneumoniae.

In this dissertation, complement activation and killing together with the antibiotic resistance of K. pneumoniae blood isolates were investigated.

In study I, it was shown that serum resistant K. pneumoniae isolates use the large polysaccharide capsule in escaping the generation of the membrane attack complex (MAC) when incubated in normal human serum (NHS), thus preventing complement mediated killing. Furthermore, this work showed activation of complement within minutes by the K. pneumoniae isolates and indicated that more than one complement activating pathway was required for complement killing of serum sensitive isolates. In Study II, 30 clinical isolates were investigated. It was demonstrated that complement activation and killing of the clinical K. pneumoniae isolates were serum concentration dependent and that C4 activation was pivotal for complement killing of K. pneumoniae. Furthermore, the alternative pathway activation was not functional in 5% NHS. Study III investigated the interactions of complement and beta-lactam antibiotics against two multi-drug resistant ESBL-producing K. pneumoniae blood isolates. This study demonstrated that serum susceptibility of the isolates was essential for synergy of beta-lactam antibiotics and serum.

In conclusion, the findings of the dissertation demonstrate that serum resistant clinical K. pneumoniae blood isolates only activate the alternative pathway. Furthermore, generation of MAC and subsequent bacterial lysis require component C4 activation. Serum resistance is an important virulence trait in ESBL-producing K. pneumoniae and synergy of beta-lactam antibiotics and serum is employed if the outer membrane is impaired.

Host

Department of Health Science and Technology, The Faulty of Medicine, Aalborg University

Address

Ph.D. Defense take place via Zoom.

More information

https://aaudk.zoom.us/j/68027261575

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