Marine Mammal Brucella Reference Strains Are Attenuated in a BALB/c Mouse Model

Abstract

Brucellosis is a zoonosis of worldwide distribution with numerous animal host species. Since the novel isolation of Brucella spp. from marine mammals in 1994 the bacteria have been isolated from various marine mammal hosts. The marine mammal reference strains Brucella pinnipedialis 12890 (harbour seal, Phoca vitulina) and Brucella ceti 12891 (harbour porpoise, Phocoena phocoena) were included in genus Brucella in 2007, however, their pathogenicity in the mouse model is pending. Herein this is evaluated in BALB/c mice with Brucella suis 1330 as a control. Both marine mammal strains were attenuated, however, B. ceti was present at higher levels than B. pinnipedialis in blood, spleen and liver throughout the infection, in addition B. suis and B. ceti were isolated from brains and faeces at times with high levels of bacteraemia. In B. suis-infected mice serum cytokines peaked at day 7. In B. pinnipedialis-infected mice, levels were similar, but peaked predominantly at day 3 and an earlier peak in spleen weight likewise implied an earlier response. The inflammatory response induced pathology in the spleen and liver. In B. ceti-infected mice, most serum cytokine levels were comparable to those in uninfected mice, consistent with a limited inflammatory response, which also was indicated by restricted spleen and liver pathology. Specific immune responses against all three strains were detected in vitro after stimulation of splenocytes from infected mice with the homologous heat-killed brucellae. Antibody responses in vivo were also induced by the three brucellae. The immunological pattern of B. ceti in combination with persistence in organs and limited pathology has heretofore not been described for other brucellae. These two marine mammal wildtype strains show an attenuated pattern in BALB/c mice only previously described for Brucella neotomea.

Brucella neotomae Recapitulates Attributes of Zoonotic Human Disease in a Murine Infection Model

“…As mentioned previously, these findings differ from the chronic lower burden of infection observed in native hosts (and humans infected with B. abortus, B. melitensis, and B. suis [1]) and from B. neotomae in the BALB/c model. Findings for B. neotomae, however, were similar to observations of BALB/c infection with the attenuated B. abortus S19 vaccine strain and Brucella ceti (7,36,37), a cetacean pathogen. S19 (7) and B. neotomae murine infection (this study) also are both associated with maximum splenic enlargement at 2 weeks.…”

Toll-Like Receptors 2 and 4 Cooperate in the Control of the Emerging Pathogen Brucella microti

“…like B. melitensis, B. abortus or B. suis or with the new ones B. ceti and B. pinnipedialis leads to a typical replication pattern in the spleen and liver, characterized by a multiplication phase until the number of bacteria reaches its maximum (acute phase), followed by a chronic plateau phase and a declining phase that ends by the clearing of the bacteria in both organs. The duration of these phases depends on the route and the dose of the inoculum and the chronic phase can last more than 20 weeks (Montaraz and Winter, 1986; Edmonds et al, 2002; Abdou et al, 2013; Nymo et al, 2016). None of the classical Brucella spp.…”

Seroprevalence for Brucella spp. in Baltic ringed seals (Phoca hispida) and East Greenland harp (Pagophilus groenlandicus) and hooded (Cystophora cristata) seals

“…Persistency, reservoirs and susceptibility have recently been addressed by several studies of Brucella. These reports have focused on environmental reservoirs, transmissions and courses and how Brucella may even persistent in macrophages and even fish (Larsen et al 2016;Nymo et al 2016aNymo et al , 2016b.…”