# Comparative Genomics of Lactococcus spp. From Global Aquaculture Outbreaks Reveals Virulence Determinants, Antibiotic Resistance, and Phage Defence Mechanisms

## TL;DR

This study finds that Lactococcus petauri is now a major cause of fish disease in aquaculture, with resistance to common antibiotics and potential for phage therapy.

## Contribution

The study identifies genomic features of Lactococcus petauri linked to virulence, antibiotic resistance, and phage defense in aquaculture outbreaks.

## Key findings

- Lactococcus petauri was the most common species in aquaculture outbreaks, not L. garvieae.
- Most isolates showed resistance to nalidixic acid and other antibiotics used in aquaculture.
- Prophage regions were common but did not carry virulence or resistance genes, but did include phage defense systems.

## Abstract

Lactococcosis is a major bacterial disease impacting rainbow trout production in South Africa and Southeast Asia, particularly during summer. In this study, 15 isolates from affected aquaculture facilities were characterised, revealing Lactococcus petauri (n = 12) as the predominant species, rather than the traditionally recognised L. garvieae (n = 3). This indicates a potential shift in the aetiology of lactococcosis with implications for diagnosis and management. Genomic screening identified multiple virulence factors, including adhesins in 14 isolates, capsular polysaccharide biosynthesis genes in 12, and sortase‐anchored proteins in all isolates, highlighting strain‐specific differences in pathogenic potential. Antimicrobial resistance (AMR) profiling revealed ermB (n = 10) and tetS (n = 11), consistent with resistance to macrolides and tetracyclines commonly applied in aquaculture. Phenotypic susceptibility testing against eight antimicrobial agents showed uniform resistance to nalidixic acid (15/15 isolates), alongside resistance to trimethoprim (12/15), sulfamethoxazole (11/15), and ciprofloxacin and oxacillin (7/15 each). These phenotypic results, while not fully aligned with the ARG profile, reflect aquaculture‐relevant antimicrobial exposures and indicate the presence of both intrinsic and acquired resistance mechanisms. Most (13/15) isolates contained 1–3 prophage regions, although none of these harboured any known virulence or AMR genes. However, they did genes encoding phage defence such as AbiD and R‐M systems. This information is important when considering the potential development of phage therapy to control piscine disease. Together, these findings advance understanding of the epidemiology, pathogenicity, and resistance dynamics of Lactococcus species in aquaculture and underscore the need for sustainable strategies to mitigate lactococcosis outbreaks.

Lactococcus petauri predominated in isolates from outbreaks of lactococcosis, suggesting a shift in disease aetiology. Genomic analysis revealed diverse virulence factors, prophage and resistance genes, while antimicrobial susceptibility testing showed uniform resistance to common antibiotics found in farming systems, emphasising the need for sustainable control strategies in aquaculture.