Bibersteinia trehalosi infections

Originally described as biotype T (trehalose fermenting) of the [Pasteurella] haemolytica complex, Bibersteinia trehalosi was recognized as a separate species (named Pasteurella trehalosi) in 1990 (Sneath and Stevens, 1990). The organism was reclassified as Bibersteinia trehalosi in 2007 on the basis of phylogenetic studies (Blackall et al., 2007).

B. trehalosi is an important pathogen of sheep, primarily associated with septicaemia in older lambs (Gilmour, 1978; Sneath and Stevens, 1990; Donachie, 2007), and less commonly with respiratory disease (Miller et al., 2011; Gonzalez et al., 2013). B. trehalosi has also been isolated from bighorn sheep with pneumonia (Rudolph et al., 2007; Wolfe et al., 2010; Drew et al., 2014) and from goats with pasteurellosis (Sanchis and Abadie, 1992; Guillou, 2004; Abadie and Thiery, 2006).

B. trehalosi has been isolated from cases of bovine respiratory disease (Collins, 2011; Cortese et al., 2012) but its role as a primary pathogen in cattle is uncertain.

The systemic form of pasteurellosis caused by B. trehalosi is characterized by fever, listlessness, poor appetite, and sudden death in young sheep. The organism is thought to move from the tonsils to the lungs and pass into the blood. This results in septicaemia and localization of the infection in one or more tissues such as the joints, udder, meninges, or lungs.

Postmortem examinations sometimes reveal subcutaneous haemorrhages over the neck and thorax, with superficial haemorrhages on the pleura, diaphragm and epicardium. The lungs may be swollen with widespread haemorrhages, and bloodstained froth in the airways, but no evidence of consolidation. Necrotic erosions are sometimes seen in the pharynx around the tonsils, nasal mucosa, oesophagus and abomasum. The tonsils and retropharyngeal lymph nodes are enlarged. The abdominal viscera are often congested; in some cases, necrotic infarcts may also be present in the liver, spleen and kidney, visible as small grey foci (Sargison, 2009).

Bibersteinia trehalosi is a common inhabitant of the upper respiratory tract and tonsils of healthy sheep. Local mucosal invasion and systemic spread are thought to follow a period of stress or management change (Dyson et al., 1981; Suàrez-Güémes et al., 1985). Stress is thought to result in corticosteroid-dependent bacterial proliferation in the tonsillar region, and injury to the alimentary tract, with consequent ulceration (Suàrez-Güémes et al., 1985). The injured pharyngeal, abomasal and duodenal mucosa serve as portals of entry for B. trehalosi derived from the tonsils. From these sites bacteria gain access to the blood as emboli, most of which impact in the capillary bed of the lungs (Dyson et al., 1981), whilst bacterial invasion of the lower alimentary tract results in primary embolization of the hepatic sinusoids (Suàrez-Güémes et al., 1985). Rapid multiplication of bacteria in these sites results in embolic dissemination to other organs and tissue. Death is attributed to endotoxaemia (Dyson et al., 1981; Suàrez-Güémes et al., 1985; Hodgson et al., 1993).

The virulence of B. trehalosi is mediated by the action of several factors, including endotoxin, adhesins, leukotoxin, and capsular polysaccharide, that afford the bacteria advantages over host immunity. The leukotoxin is particularly important in pathogenesis (Subramaniam et al., 2014). Typically, domestic sheep carry leukotoxin-positive Mannheimia haemolytica and/or B. trehalosi as commensal bacteria in their nasopharynx. In contrast, most bighorn sheep do not carry leukotoxin-positive M. haemolytica or B. trehalosi, or carry leukotoxin-negative strains in their nasopharynx (Subramaniam et al., 2014).

Dassanayake et al. (2010) describe the interaction between B. trehalosi and M. haemolytica. The authors point out that although B. trehalosi is commonly isolated from cases of pneumonia in bighorn sheep, M. haemolytica is the only pathogen that has consistently been shown to cause bronchopneumonia and death under experimental conditions. Other studies show that only leukotoxin-producing strains of B. trehalosi can cause pneumonia (Dassanayake et al., 2013). As a result, there is some question as to whether or not B. trehalosi is likely to be a major cause of pneumonia in bighorn sheep. Research by the authors shows that B. trehalosi replicates at almost twice the rate of M. haemolytica and is able to inhibit and overgrow M. haemolytica. This data would lead to speculation that, in many cases, M. haemolytica might be the initial cause of pneumonia but is then overgrown by B. trehalosi, which is the organism subsequently isolated.

Although B. trehalosi infections are considered rare in cattle, B. trehalosi is sometimes isolated from cattle with respiratory disease and reports seem to be increasing (Collins, 2011). Cortese et al. (2012) reported severe non-responsive bovine respiratory disease (BRD) outbreaks associated with multidrug-resistant B. trehalosi.

To evaluate the role of B. trehalosi in BRD, Hanthorn et al. (2014) used an intra-tracheal inoculation model in calves. They found that B. trehalosi-inoculated calves did not have increased lung involvement compared to control calves and concluded that B. trehalosi may not be a primary pathogen of respiratory disease in cattle. Culture of B. trehalosi from diagnostic submissions should not be immediately identified as a primary cause of respiratory disease, they say. They speculate that the main role of B. trehalosi in BRD may be as secondary and perhaps opportunistic bacteria.

B. trehalosi has been identified as the cause of necrotizing hepatitis/sudden death in an adult cow (Watson and Scholes, 2010). Spagnoli et al. (2011) describe a case of subcutaneous botryomycosis caused by B. trehalosi in a Texas Longhorn steer.

Although sheep of any age are susceptible to systemic pasteurellosis, animals five to 12 months old are at greatest risk (Dyson et al., 1981; Ellis, 1984). Prevalence increases in cold, wet weather conditions (Dyson et al., 1981). Stress associated with weaning, transportation, vaccination and shearing, as well as a change in diet, are thought to be predisposing factors (Suarez-Guemes, 1983; Suàrez-Güémes et al., 1985; Mackie et al., 1995). Concurrent diseases such as cobalt deficiency or tickborne fever (caused by Anaplasma phagocytophilum) may also predispose to outbreaks of the disease (Sargison, 2009; Daniel et al., 2015).

Antimicrobials effective against gram-negative bacteria, such as ampicillin, amoxicillin-clavulinic acid, ceftiofur, oxytetracycline and florfenicol, can potentially be used to treat B. trehalosi infections, although strains vary in their susceptibility (Richard et al., 1992; Sanchis and Abadie, 1992; Weiser et al., 2009; Scott, 2011). However, sheep are rarely seen in the early stages of the disease and treatment is only successful if begun very early in the disease process due to rapid progression of lung damage and endotoxin release. Parenteral fluids and anti-inflammatory agents are important adjuncts to antibiotic therapy (Scott, 2011).

The presence of antimicrobial resistance genes in B. trehalosi was first reported by Kehrenberg et al. (2006) in a florfenicol-resistant isolate from a calf. They found that resistance to chloramphenicol and florfenicol were associated with a plasmid which also carried functionally active genes for resistance to sulphonamides.