Preprint:

Dual-use virulence factors of the opportunistic pathogen Chromobacterium haemolyticum mediate haemolysis and colonization.

Dumjahn L, Wein P, Molloy EM, Scherlach K, Trottmann F, Meisinger P, Judd LM, Pidot SJ, Stinear TP, Richter I, Hertweck C (2025) Dual-use virulence factors of the opportunistic pathogen Chromobacterium haemolyticum mediate haemolysis and colonization. bioRxiv [Preprint]

Abstract

Chromobacterium haemolyticum is an environmental bacterium that can cause severe and fatal opportunistic infections in humans and animals. Although C. haemolyticum is characterized by its strong β-haemolytic activity, the molecular basis of this phenotype has remained elusive over the more than fifteen years since the species was first described. Here, we report the discovery of a family of cyclic lipodepsipeptides that are responsible for the potent haemolytic activity of C. haemolyticum. Comparative genomics of Chromobacterium spp. isolated from different environments revealed a completely conserved gene locus (chl) encoding a non-ribosomal peptide synthetase (NRPS). Metabolic profiling of C. haemolyticum DSM 19808 identified a suite of cyclic lipodepsipeptides as the products of the chl locus, with the three main congeners (jagaricin, chromolysin A and B) being elucidated by a combination of tandem mass spectrometry, chemical derivatization, and NMR spectroscopy. Significantly, a C. haemolyticum chl deletion mutant is devoid of haemolytic activity. Moreover, purified jagaricin, chromolysin A and B are haemolytic at low- micromolar concentrations in an erythrocyte lysis assay. Further bioassays demonstrated that the cyclic lipodepsipeptides are crucial for biofilm-forming and swarming behavior of C. haemolyticum. MALDI mass spectrometry imaging showed that primarily chromolysin A and B are involved in these processes in vitro. Our data shed light on the bioactivities of chromolysin A and B, specialized metabolites that likely contribute to both successful colonization of new niches and virulence potential of C. haemolyticum.

Leibniz-HKI-Authors

Leo Dumjahn
Christian Hertweck
Philippe Meisinger
Evelyn Molloy
Ingrid Richter
Kirstin Scherlach
Felix Trottmann
Philipp Wein

Identifier

doi: 10.1101/2025.01.10.632398