We review the molecular and epidemiological characteristics of cetacean morbillivirus (CeMV) and the diagnosis and pathogenesis of associated disease, with six different strains detected in cetaceans worldwide. CeMV has caused epidemics with high mortality in odontocetes in Europe, the USA and Australia. It represents a distinct species within the Morbillivirus genus. Although most CeMV strains are phylogenetically closely related, recent data indicate that morbilliviruses recovered from Indo-Pacific bottlenose dolphins (Tursiops aduncus), from Western Australia, and a Guiana dolphin (Sotalia guianensis), from Brazil, are divergent. The signaling lymphocyte activation molecule (SLAM) cell receptor for CeMV has been characterized in cetaceans. It shares higher amino acid identity with the ruminant SLAM than with the receptors of carnivores or humans, reflecting the evolutionary history of these mammalian taxa. In Delphinidae, three amino acid substitutions may result in a higher affinity for the virus. Infection is diagnosed by histology, immunohistochemistry, virus isolation, RT-PCR, and serology. Classical CeMV-associated lesions include bronchointerstitial pneumonia, encephalitis, syncytia, and lymphoid depletion associated with immunosuppression. Cetaceans that survive the acute disease may develop fatal secondary infections and chronic encephalitis. Endemically infected, gregarious odontocetes probably serve as reservoirs and vectors. Transmission likely occurs through the inhalation of aerosolized virus but mother to fetus transmission was also reported.

Since 2006, there has been a marked increase in the number of reports of severe and often fatal fungal skin infections in wild snakes in the eastern USA. The emerging condition, referred to as snake fungal disease (SFD), was initially documented in rattlesnakes, where the infections were believed to pose a risk to the viability of affected populations. The disease is caused by Ophidiomyces ophiodiicola , a fungus recently split from a complex of fungi long referred to as the Chrysosporium anamorph of Nannizziopsis vriesii (CANV). Here we review the current state of knowledge about O. ophiodiicola and SFD. In addition, we provide original findings which demonstrate that O. ophiodiicola is widely distributed in eastern North America, has a broad host range, is the predominant cause of fungal skin infections in wild snakes and often causes mild infections in snakes emerging from hibernation. This new information, together with what is already available in the scientific literature, advances our knowledge of the cause, pathogenesis and ecology of SFD. However, additional research is necessary to elucidate the factors driving the emergence of this disease and develop strategies to mitigate its impacts. This article is part of the themed issue ‘Tackling emerging fungal threats to animal health, food security and ecosystem resilience’.

A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.

The aim of this study of serpentovirus infection in captive snakes was to assess the susceptibility of different types of snakes to infection and disease, to survey viral genetic diversity, and to evaluate management practices that may limit infection and disease. Antemortem oral swabs were collected from 639 snakes from 12 US collections, including 62 species, 28 genera, and 6 families: Pythonidae (N = 414 snakes; pythons were overrepresented in the sample population), Boidae (79), Colubridae (116), Lamprophiidae (4), Elapidae (12), and Viperidae (14). Infection was more common in pythons (38%; 95% CI: 33.1–42.4%), and in boas (10%; 95% CI: 5.2–18.7%) than in colubrids (0.9%, 95% CI: <0.01–4.7%); infection was not detected in other snake families (lamprophiids 0/4, 95% CI: 0–49%; elapids 0/12, 95% CI: 0–24.2%; and vipers 0/14, 95% CI: 0–21.5%), but more of these snakes need to be tested to confirm these findings. Clinical signs of respiratory disease were common in infected pythons (85 of 144). Respiratory signs were only observed in 1 of 8 infected boas and were absent in the single infected colubrid. Divergent serpentoviruses were detected in pythons, boas, and colubrids, suggesting that different serpentoviruses might vary in their ability to infect snakes of different families. Older snakes were more likely to be infected than younger snakes (p-value < 0.001) but males and females were equally likely to be infected (female prevalence: 23.4%, 95% CI 18.7–28.9%; male prevalence: 23.5%, 95% CI 18–30.1%; p-value = 0.144). Neither age (p-value = 0.32) nor sex (p-value = 0.06) was statistically associated with disease severity. Longitudinal sampling of pythons in a single collection over 28 months revealed serpentovirus infection is persistent, and viral clearance was not observed. In this collection, infection was associated with significantly increased rates of mortality (p-value = 0.001) with death of 75% of infected pythons and no uninfected pythons over this period. Offspring of infected parents were followed: vertical transmission either does not occur or occurs with a much lower efficiency than horizontal transmission. Overall, these findings confirm that serpentoviruses pose a significant threat to the health of captive python populations and can cause infection in boa and colubrid species.

The resurgence of tuberculosis has been characterized by the emergence of significant numbers of drug-resistant strains. Furthermore, microorganisms of the Mycobacterium avium complex, opportunistic pathogens common in AIDS patients, are inherently resistant to many traditional antimycobacterial agents (20,23). Hence, the development of novel drugs for the treatment of atypical infections by M. avium, Mycobacterium intracellulare, and multiple-drug-resistant Mycobacterium tuberculosis is urgently needed.The mycobacterial cell wall is an effective barrier that contributes to drug resistance (45). Inhibitors of cell wall biosynthesis not only are potential antimycobacterial agents but also increase mycobacterial susceptibility to other antimicrobial agents ( (26,31,33). Moreover, the biosynthesis of mycolyl-arabinogalactan-peptidoglycan complex is inhibited by DCS in M. tuberculosis (10), and biochemical studies indicated that D-alanine ligase is one of the targets in mycobacteria (11).DCS is an effective antimycobacterial agent but is rarely prescribed and used only in combined therapies due to its adverse effects (21,22,54). These side effects are due to binding of DCS to neuronal N-methyl aspartate receptors (44) and inhibition of enzymes that metabolize and synthesize the neurotransmitter ␥-aminobutyric acid (53). Nevertheless, DCS is an excellent candidate for the development of a new generation of antibiotics. Two important considerations predict that rationally designed derivatives of DCS may be more efficacious antimicrobial agents. First, DCS targets participate in essential steps of cell wall synthesis. Second, DCS resistance has not yet become an important clinical problem. Therefore, the identification of DCS targets and the elucidation of the mechanisms leading to DCS resistance may contribute to the development of new therapeutics with fewer side effects and mechanisms of action which do not favor the emergence of resistance.Few studies on the mode of action and mechanisms of DCS resistance in mycobacteria have been conducted. David (9) isolated and characterized step-wise DCS-resistant (DCS r ) mutants of M. tuberculosis and discovered mutants that showed either normal or reduced cellular permeability to DCS. It was hypothesized that mutants with normal uptake carried mutations in the D-alanine ligase gene, but no biochemical or molecular evidence in support of this hypothesis was provided.Here we describe the first molecular genetic analysis of DCS resistance in mycobacteria, which led to the identification of one of the DCS targets and resistance mechanisms in Mycobacterium smegmatis. A spontaneous DCS r mutant strain of M. smegmatis exhibited a promoter-up mutation in the D-alanine racemase gene (alrA) which increased the levels of expression