Both clinical and environmentalCaulobacterspecies act as opportunistic pathogens
Authors: Moore Gabriel M. , Gitai Zemer 
Published: May 2019

TheCaulobactergenus, including the widely-studied model organismCaulobacter crescentus, has been thought to be non-pathogenic and thus proposed as a bioengineering vector for various environmental remediation and medical purposes. However,Caulobacterspecies have been implicated as the causative agents of several hospital-acquired infections, raising the question of whether these clinical isolates represent an emerging pathogenic species or whetherCaulobacterson whole possess previously-unappreciated virulence capability. Given the proposed environmental and medical applications forC. crescentus, understanding the potential pathogenicity and human health implications of this bacterium is crucial. Consequently, we sequenced a clinicalCaulobacterisolate to determine if it has acquired novel virulence determinants. We found that the clinical isolate represents a new species,Caulobacter mirare. C. mirarephylogenetically resembles bothC. crescentusand the relatedC. segnis, which was also thought to be non-pathogenic. The similarity to otherCaulobactersand lack of obvious pathogenesis markers suggested thatC. mirareis not unique amongstCaulobactersand that consequently otherCaulobactersmay also have the potential to be virulent. We tested this hypothesis by characterizing the ability ofCaulobactersto infect the model animal hostGalleria mellonella. In this context, two different lab strains ofC. crescentusproved to be as pathogenic asC. mirare, while lab strains ofE. coliwere non-pathogenic. Further characterization showed thatCaulobacterpathogenesis is mediated by a dose-dependent, cell-associated toxic factor that does not require active bacterial cells or host cellular innate immunity to elicit its toxic effects. Finally, we show thatC. crescentusdoes not grow well in standard clinical culture conditions, suggesting thatCaulobacterinfections may be more common than generally appreciated but rarely cultured. Taken together, our findings redefineCaulobactersas opportunistic pathogens and highlight the importance of broadening our methods for identifying and characterizing pathogens.

AUTHOR SUMMARY

Bacterial species have historically been classified as either capable of causing disease in an animal (pathogenic) or not.Caulobacterspecies represent a class of bacteria that were thought to be non-pathogenic.Caulobactershave been widely studied and proposed to be used for various industrial and medical applications due to their presumed safety. However, recent reports of humanCaulobacterinfections raised the question of whether disease-causingCaulobactershave acquired special factors that help them cause disease or whether the ability to infect is a more general feature of mostCaulobacters. By combining genomic sequencing and animal infection studies we show that a clinicalCaulobacterstrain is similar to labCaulobactersand that allCaulobactersstudied can infect a model host. We explore the mechanism of this infectivity and show that it is due to a toxic factor that associates withCaulobactercells. We also provide a possible explanation for whyCaulobactershave not traditionally been isolated from human patients, owing to their inability to tolerate the salt levels used in most medical culturing systems.