PMID- 33372837 OWN - NLM STAT- MEDLINE DCOM- 20210924 LR - 20210924 IS - 2150-5608 (Electronic) IS - 2150-5594 (Print) IS - 2150-5594 (Linking) VI - 12 IP - 1 DP - 2021 Dec TI - Bordetella bronchiseptica promotes adherence, colonization, and cytotoxicity of Streptococcus suis in a porcine precision-cut lung slice model. PG - 84-95 LID - 10.1080/21505594.2020.1858604 [doi] AB - Bordetella (B.) bronchiseptica and Streptococcus (S.) suis are major pathogens in pigs, which are frequently isolated from co-infections in the respiratory tract and contribute to the porcine respiratory disease complex (PRDC). Despite the high impact of co-infections on respiratory diseases of swine (and other hosts), very little is known about pathogen-pathogen-host interactions and the mechanisms of pathogenesis. In the present study, we established a porcine precision-cut lung slice (PCLS) model to analyze the effects of B. bronchiseptica infection on adherence, colonization, and cytotoxic effects of S. suis. We hypothesized that induction of ciliostasis by a clinical isolate of B. bronchiseptica may promote subsequent infection with a virulent S. suis serotype 2 strain. To investigate this theory, we monitored the ciliary activity by light microscopy, measured the release of lactate dehydrogenase, and calculated the number of PCLS-associated bacteria. To study the role of the pore-forming toxin suilysin (SLY) in S. suis-induced cytotoxicity, we included a SLY-negative isogenic mutant and the complemented mutant strain. Furthermore, we analyzed infected PCLS by histopathology, immunofluorescence microscopy, and field emission scanning electron microscopy. Our results showed that pre-infection with B. bronchiseptica promoted adherence, colonization, and, as a consequence of the increased colonization, the cytotoxic effects of S. suis, probably by reduction of the ciliary activity. Moreover, cytotoxicity induced by S. suis is strictly dependent on the presence of SLY. Though the underlying molecular mechanisms remain to be fully clarified, our results clearly support the hypothesis that B. bronchiseptica paves the way for S. suis infection. FAU - Votsch, Desiree AU - Votsch D AD - Institute for Microbiology, University of Veterinary Medicine Hannover , Hannover, Germany. FAU - Willenborg, Maren AU - Willenborg M AD - Institute for Microbiology, University of Veterinary Medicine Hannover , Hannover, Germany. FAU - Baumgartner, Wolfgang AU - Baumgartner W AD - Institute for Pathology, University of Veterinary Medicine Hannover , Hannover, Germany. FAU - Rohde, Manfred AU - Rohde M AD - Central Facility for Microscopy, Helmholtz Center for Infection Research , Braunschweig, Germany. FAU - Valentin-Weigand, Peter AU - Valentin-Weigand P AD - Institute for Microbiology, University of Veterinary Medicine Hannover , Hannover, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Virulence JT - Virulence JID - 101531386 RN - 0 (Hemolysin Proteins) RN - 0 (suilysin) SB - IM MH - Animals MH - *Bacterial Adhesion MH - Bordetella bronchiseptica/genetics/*metabolism/*pathogenicity MH - Cilia/metabolism MH - Coinfection MH - Hemolysin Proteins/genetics MH - *Host-Pathogen Interactions MH - In Vitro Techniques MH - Lung/*microbiology MH - Streptococcus suis/metabolism/*pathogenicity MH - Swine MH - Swine Diseases/microbiology PMC - PMC7781633 OTO - NOTNLM OT - Bordetella bronchiseptica OT - Streptococcus suis OT - PRDC OT - porcine precision-cut lung slices OT - porcine respiratory tract infection OT - respiratory co-infection OT - suilysin COIS- The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of the data, in the writing of the manuscript, or in the decision to publish the results. EDAT- 2020/12/30 06:00 MHDA- 2021/09/25 06:00 PMCR- 2020/12/29 CRDT- 2020/12/29 12:08 PHST- 2020/12/29 12:08 [entrez] PHST- 2020/12/30 06:00 [pubmed] PHST- 2021/09/25 06:00 [medline] PHST- 2020/12/29 00:00 [pmc-release] AID - 1858604 [pii] AID - 10.1080/21505594.2020.1858604 [doi] PST - ppublish SO - Virulence. 2021 Dec;12(1):84-95. doi: 10.1080/21505594.2020.1858604.