Human pulmonary infection by Brucella suis vaccine strain S2 revealed by genome sequencing in China

Brucellosis the most common zoonosis worldwide. For control and prevention of animal brucellosis, various Brucella vaccines have been developed. Brucella suis S2, a live attenuated vaccine strain proven safe to humans, is widely used in China. In this report, a 77-year-old woman with a history of coughing and expectoration for three years was diagnosed with brucellosis by next-generation sequencing. Subsequently, the Brucella isolate from this patient was determined to be Brucella suis vaccine strain S2 by phage lysis experiments, quantitative real-time PCR, and third-generation sequencing. Its nucleotide identity with vaccine strain S2 was as high as 99.9996%, and only 14 deletion/insertion mutations or single nucleotide polymorphisms were detected. A phylogenetic tree constructed based on the genome sequences revealed that this strain clustered together with strain S2. As the patient denied having a history of contact with animals or exposure to other known sources, an epidemiological investigation was carried out on environmental and food samples. The results did not reveal a clear infection source except for a B. suis S2-like strain (99.9939% identity to B. suis S2 strain) from a milk sample. Our study may provide the first reliable evidence that B. suis vaccine strain S2 has the potential to infect humans. While this needs further confirmation, it points to the need to survey the virulence and risks of vaccine strain S2 in humans. In addition, the route of transmission of vaccine strain S2 still needs to be clarified to prevent more cases of brucellosis originating from this strain.