Streptococcus agalactiae infection in zebrafish larvae

Abstract

Streptococcus agalactiae (Group B Streptococcus, GBS) is an encapsulated, Gram-positive bacterium that is a leading cause of neonatal pneumonia, sepsis and meningitis, and an emerging aquaculture pathogen. The zebrafish (Danio rerio) is a genetically tractable model vertebrate that has been used to analyze the pathogenesis of both aquatic and human bacterial pathogens. We have developed a larval zebrafish model of GBS infection to study bacterial and host factors that contribute to disease progression. GBS infection resulted in dose dependent larval death, and GBS serotype III, ST-17 strain was observed as the most virulent. Virulence was dependent on the presence of the GBS capsule, surface anchored lipoteichoic acid (LTA) and toxin production, as infection with GBS mutants lacking these factors resulted in little to no mortality. Additionally, interleukin-1β il1b and CXCL-8 (cxcl8a) were significantly induced following GBS infection compared to controls. We also visualized GBS outside the brain vasculature, suggesting GBS penetration into the brain during the course of infection. Our data demonstrate that zebrafish larvae are a valuable model organism to study GBS pathogenesis.

Bacterial induction of Snail1 contributes to blood-brain barrier disruption

“…To further examine the role of snai1a in vivo, we developed a larval model of zebrafish GBS infection (34). We generated Tg(HSP:dn-snai1a) animals that function as a dominant-negative inhibitor of endogenous snai1a.…”

“…Larval zebrafish model of GBS infection. Infection assays were performed as described previously (34). Briefly, zebrafish larvae at 3 dpf were anesthetized with tricane and placed on a 2% agar plate for stabilization.…”

Zebrafish and Streptococcal Infections

“…Therefore, zebrafish embryos at 2–3 dpf are usually used in the streptococcal infection experiments. The most common inoculation sites of 2‐ to 3‐day‐old zebrafish include the circulation valley, for example, which leads to a systemic bacterial spread, while injection into the otic vesicle or tail muscle (7 dpf) causes a local infection . The injection routes commonly used in streptococcal infections are shown in Fig.…”

“…The complex interactions occurring between the host and the pathogen are best studied in their natural environment, where the mechanisms for both the host defence and the pathogen evasion have evolved. The zebrafish provides a natural niche for some streptococci, including S. iniae and S. agalactiae , and this connection has been exploited in the development of streptococcus–zebrafish models to be used to reveal the detailed mechanisms of infections threatening human health . The information gained from the studies using zoonotic streptococci has the potential to reveal novel treatment and vaccination strategies that could be used in both human clinics and aquaculture.…”

Galleria mellonellaas an infection model for the multi-host pathogenStreptococcus agalactiaereflects hypervirulence of ST283

“…A number of in vivo models exists for GBS infection (mice, rats, zebra fish) and are valuable for the study of host-pathogen interactions and virulence 20,21,22 . In the last few years, larvae of the greater wax moth (Galleria mellonella) have been used as an alternate infection model for several human and non-human bacterial pathogens such as Pseudomonas aeruginosa 23 , Bacillus cereus 24 , Listeria monocytogenes 25,26 , Vibrio anguillarum 27 and Clostridium difficile 28 .…”