Salmonella re-engineers the intestinal environment to break colonization resistance in the presence of a compositionally intact microbiota.

The gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms. Using metabolite profiling and genetic analysis, we show that the initial rise in luminal pathogen abundance was powered by a combination of aerobic respiration and mixed acid fermentation of simple sugars, such as glucose, which resulted in their depletion from the metabolome. The initial rise in the abundance of the pathogen in the feces coincided with a reduction in the cecal concentrations of acetate and butyrate and an increase in epithelial oxygenation. Notably, these changes in the host environment preceded changes in the microbiota composition. We conclude that changes in the host environment can weaken colonization resistance even in the absence of overt compositional changes in the gut microbiota.

Granulomatous meningoencephalitis and blindness associated with Mycobacterium tuberculosis complex infection in a senile female chimpanzee (Pan troglodytes).

A 40-year old female chimpanzee (Pan troglodytes) developed hyporexia, weight loss, followed by progressive and complete blindness. Tomography demonstrated an intracranial mass in the rostroventral brain involving the optic chiasm, with a presumptive diagnosis of neoplasm. However, histopathology revealed a granulomatous meningoencephalitis, and tissue samples tested positive for Mycobacterium tuberculosis.

Cell and Tissue Tropism of Brucella spp.

Brucella spp. are facultatively intracellular bacteria that can infect, survive, and multiply in various host cell types in vivo and/or in vitro. The genus Brucella has markedly expanded in recent years with the identification of novel species and hosts, which has revealed additional information about the cell and tissue tropism of these pathogens. Classically, Brucella spp. are considered to have tropism for organs that contain large populations of phagocytes such as lymph nodes, spleen, and liver, as well as for organs of the genital system, including the uterus, epididymis, testis, and placenta. However, experimental infections of several different cultured cell types indicate that Brucella may actually have a broader cell tropism than previously thought. Indeed, recent studies indicate that certain Brucella species in particular hosts may display a pantropic distribution in vivo. This review discusses the available knowledge on cell and tissue tropism of Brucella spp. in natural infections of various host species, as well as in experimental animal models and cultured cells.

Polyarteritis nodosa in a captive common wooly monkey (Lagothrix lagotricha) associated with intestinal necrosis, peritonitis, and sepsis.

Polyarteritis nodosa is an idiopathic necrotizing vasculitis that affects small to medium-sized arteries. We describe a case of polyarteritis nodosa in a captive common wooly monkey (Lagothrix lagotricha) associated with transmural intestinal necrosis and secondary peritonitis. This condition must be considered for differential diagnosis of segmental arteritis in neotropical primates.

Influence of landscape ecology and physiological implications in bats from different trophic guilds.

Bats may serve as bioindicators of human impact on landscape ecology. This study aimed to evaluate the health condition of bats from different food guilds captured in two areas with different land use profiles in Brazil and to compare data on the oxidant-antioxidant balance and histopathological changes due to different anthropogenic pressures. Bats were collected from a protected area in Serra do Cipó National Park (SCNP), MG, Brazil, and an area with intense agricultural activity in the municipality of Uberaba (UB), MG, Brazil. Despite the differences in land use and occupation between the studied areas, bats showed similar responses. However, the trophic guilds were affected differently. Frugivorous bats in both areas showed lower activities of the enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) and concentrations of malondialdehyde (MDA) than other guilds, which can be explained by the greater intake of antioxidants from the diet in addition to the lower production of reactive oxygen species (ROS). Histopathological analysis of the livers revealed that the animals had a similar prevalence in the two areas, with some differences related to guilds. Compared with other bats, hematophagous bats from SCNP had a higher prevalence of steatosis and, together with frugivorous bats from Uberaba, had higher frequencies of ballooning degeneration, suggesting that these animals are subjected to anthropogenic factors capable of inducing disturbances in hepatic metabolism. Hematophagous bats from Uberaba had a higher prevalence of portal inflammation, while insectivorous bats from Uberaba had a higher prevalence of lobular and portal inflammation. The profiles of use and occupation of the areas are different; Uberaba bats seem to face worse conditions because they show more liver damage owing to lipoperoxidation.

Lethal acute diarrhea associated with Clostridioides difficile toxin A and B in a buffy-tufted-ear marmoset (Callithrix aurita).

This is a case of lethal acute diarrhea associated with a mild neutrophilic enteritis in a buffy-tufted-ear marmoset (Callithrix aurita) with detection of A/B toxins and isolation of a toxigenic clade 3 Clostridioides difficile strain (A+ B+ CDT+ , ST5), which should be considered as a potential cause of enteritis in this species.

Pathogenesis of Brucella ovis in pregnant mice and protection induced by the candidate vaccine strain B. Ovis ΔabcBA.

Ovine brucellosis caused by Brucella ovis is a major cause of reproductive failure in sheep. This study aimed to evaluate transplacental infection and pathogenicity of B.ovis wild type strain ATCC 25,840 (WT B.ovis) and the candidate vaccine strain B.ovis ΔabcBA in pregnant mice. A total of 40 BALB/c mice were equally divided into 4 groups: (i) non immunized and uninfected control mice (3/10 mice became pregnant); (ii) non immunized and challenged with WT B.ovis (5/10 pregnant); (iii) inoculated only with B.ovis ΔabcBA (6/10 pregnant); (iv) immunized with B.ovis ΔabcBA and challenged with WT B.ovis (5/10 pregnant). Female mice bred, and five days after visualization of the vaginal plug, they were inoculated intraperitoneally (ip) with 100 µL of sterile PBS, 100 µL of 1 × 106 CFU of B.ovis ΔabcBA, or 100 µL of 1 × 106 CFU of B.ovis WT, according to each group. At the 17th day of gestation, samples of spleen, liver, uterus, placenta, fetus and mammary gland were obtained for bacteriology, histopathology and immunohistochemistry. Non immunized mice challenged with B.ovis WT developed necrotizing placentitis as well as microgranulomas in the liver and spleen. These findings support the notion that B.ovis infection in pregnant mice induces lesions that are similar to those caused by B.abortus in the same animal model. B.ovis ΔabcBA was not recovered from any of the sampled organs, and it did not cause any gross or microscopic lesions, indicating that it is a safe and attenuated strain in this experimental model. In addition, B.ovis ΔabcBA was induced protective immunity as demonstrated by decreased numbers of B.ovis WT in the liver, uterus and fetuses of immunized mice after the challenge with B.ovis WT.

Mammaliicoccus (Staphylococcus) sciuri-induced suppurative meningoencephalitis and bacteremia in an infant western lowland gorilla (Gorilla gorilla gorilla).

Mammaliicoccus (Staphylococcus) sciuri has been rarely associated with infections and sepsis in humans. A 3-month-old male western lowland gorilla (Gorilla gorilla gorilla), born under human care, died after a traumatic event. Histologic, microbiologic, and molecular findings in postmortem demonstrated a suppurative meningoencephalitis and bacteremia associated with M. sciuri infection.

Streptococcus pasteurianus-induced valvular endocarditis and sepsis in a puerperal emperor tamarin (Saguinus imperator).

Streptococcus pasteurianus is associated with endocarditis and sepsis in humans. A puerperal emperor tamarin died, and necropsy showed a bacterial endocarditis with sepsis. DNA sequencing from the paraffinized heart tissue was compatible with S. pasteurianus. S. pasteurianus could be an important agent associated with sepsis in tamarins.

Natural cururu toad (Rhinella sp.) poisoning in a free-ranging lesser grison (Galictis cuja): Outcomes in a new susceptible predator with a novel peptide description.

Cururu toad (Rhinella marina group) is widely distributed in Brazil. Lesser grison (Galitic cuja) is a South American mustelid. This is the first report of natural poisoning in a free-ranging lesser grison by Rhinella toad parotoid gland secretion (PGS). Five minutes after biting a toad, the lesser grison developed convulsion, dying within 1.5 h. Mass spectrometry analysis of a milky-whitish secretion found in the lesser grison oral cavity allowed identification of a bufotoxin and a new bufonid peptide.

Histopathologic and immunophenotypic profile of a spontaneous mammary carcinoma in a male Humboldt's white-fronted capuchin (Cebus albifrons).

A 20-year-old male captive Humboldt's white-fronted capuchin (Cebus albifrons) that died accidentally had a small non-ulcerative mammary nodule diagnosed as a mammary carcinoma. Immunohistochemistry demonstrated that neoplastic cells were positive for pan-cytokeratin and cytokeratin-7. Approximately 20% of neoplastic cells were positive for Ki-67. Neoplastic cells expressed estrogen and progesterone receptors.

Epidemiological, clinical and pathological aspects of lethal acanthocephalosis in captive neotropical primates.

BACKGROUND: Acanthocephalosis is an important cause of death in captive New World primates (NWP). Once established in a colony, it is extremely difficult to treat and control, quickly spreading among NWP with a high mortality rate. This study aimed to characterize the disease associated with infection with acanthocephalans according to its epidemiological, clinical, and anatomopathological aspects in a captive NWP population. METHODS: From 2010 to 2020, a Brazilian zoo had recurrent deaths of NWP associated to acanthocephalan parasitism. Clinical and pathological profiles of these animals were analyzed considering the host species, sex, age, weight, clinical signs, therapeutic protocols, and pathological findings. RESULTS: A total of 27 deaths associated with acanthocephalosis were recorded, all lethal cases affected tamarins and lion tamarins, corresponding to 67.5% of total deaths during the course of this study. Ten animals died with no previously detected clinical signs, whereas cases with noticeable clinical signs often had apathy and progressive weight loss, resulting in cachexia. Symptomatic NWP were treated with anthelmintic protocols, antibiotics, and support therapy. However, all hospitalized animals died and had grossly detectable adult acanthocephalans in the intestinal lumen that were identified as Prosthenorchis sp., which were associated with transmural and ulcerative enteritis. CONCLUSIONS: This report revealed the impact of acanthocephalosis in a naturally infected captive colony of NWP, particularly affecting tamarins (Saguinus spp.) and lion tamarins (Leontopithecus spp.), with failed treatment and control strategies.

ACUTE NECROTIZING AND EOSINOPHILIC MYOCARDITIS IN A CHIMPANZEE (PAN TROGLODYTES).

Cardiac disease is of importance in captive chimpanzee (Pan troglodytes) health. Here we report an eosinophilic and necrotizing myocarditis in a 17-y-old chimpanzee with no previous history of cardiac disease that progressed to death within 48 h. Toxic and infectious causes were ruled out. The chimpanzee had eosinophilia at different occasions in previous years. The animal had a severe, diffuse, and acute monophasic necrotizing myocarditis, with a moderate lymphoplasmacytic infiltrate that was rich in eosinophils. Ante- and postmortem investigations are compatible with an unusual eosinophilic myocarditis with clinical evolution and morphology comparable with human eosinophilic myocarditis secondary to hypereosinophilic syndrome.

Polyostotic osteosarcoma associated with avian leukosis virus infection in a captive bare-faced curassow (Crax fasciolata).

BACKGROUND: Osteosarcoma is a malignant mesenchymal bone tumor. Although it is a common tumor in the appendicular skeleton of dogs and cats, it is rarely reported in birds. Retroviruses are usually associated with solid tumor development in different avian species. CASE PRESENTATION: This report aims to describe a case of osteosarcoma associated with the avian leukosis virus in a captive bare-faced curassow (Crax fasciolata). A captive adult female bare-faced curassow presented with lameness, hyporexia, and a non-ulcerative and firm tumor in the right femur. The bird was euthanized due to the poor prognosis. Histopathology revealed an infiltrative mesenchymal neoplasm consisting of spindle cells with moderate cell pleomorphism, organized in bundles and interspersed by marked deposition of the osteoid matrix, which was compatible with osteosarcoma affecting both femur and tibiotarsus, with renal metastasis. Immunohistochemistry of the primary and metastatic tumor demonstrated vimentin expression by neoplastic cells. Samples of the neoplasm, bone marrow, and spleen were processed for PCR, which enabled the demonstration of proviral avian leukosis virus (ALV) DNA. CONCLUSIONS: To the best of our knowledge, this is the first report of an osteosarcoma in a bare-faced curassow with an unusual polyostotic manifestation and associated with ALV infection.

Genotyping of Toxoplasma gondii in a lethal toxoplasmosis outbreak affecting captive howler monkeys (Alouatta sp.).

BACKGROUND: Toxoplasmosis is a zoonotic disease that affects humans and warm-blooded animals. This study describes an outbreak of toxoplasmosis in howler monkeys (Alouatta sp.) and survival of capuchins (Sapajus apella), under the same environmental conditions. METHODS: Howler monkeys were submitted to post-mortem examination. Tissue samples were processed to histopathology and immunohistochemistry to detect lesions and tachyzoites of Toxoplasma gondii. Tissue samples were also frozen and submitted to PCR and genotyping of T. gondii. RESULTS: Typical lesions were observed in several organs including the liver, lymph node, and brain, with intralesional cysts and tachyzoites of T. gondii demonstrated by immunohistochemistry. T. gondii genomic sequences were amplified by PCR, and genotyping characterized the same T. gondii clone in all howler monkeys. CONCLUSIONS: Our results support the notion that some species of neotropical primates are highly susceptible to toxoplasmosis and the hypothesis that capuchins (S. apella) may be resistant.

Histopathologic Patterns and Susceptibility of Neotropical Primates Naturally Infected With Yellow Fever Virus.

Yellow fever is an important zoonotic viral disease that can be fatal for both human and nonhuman primates. We evaluated histopathologic changes in free-ranging neotropical primates naturally infected with yellow fever virus (YFV) compared with uninfected cohorts. The most frequent lesions in primates infected with YFV were hepatic changes characterized by midzonal necrosis with lipidosis and mild inflammation including lymphocytes, macrophages, plasma cells, and infrequently neutrophils. Importantly, severe necrotizing hepatic lesions were often observed in Alouatta sp. (howler monkeys), whereas Callithrix sp. (common marmosets) had nearly no hepatic changes. Moderate to severe hepatic necrosis was present in 21/23 (91%) of the YFV-positive Alouatta sp. compared with 10/29 (34%) of the YFV-positive Callithrix sp. (P < .0001; odds ratio = 20). Similarly, hepatitis was more intense in Alouatta sp. compared with Callithrix sp. Furthermore, the frequency of YFV infection was significantly higher in Alouatta sp. compared with Callithrix sp. or Sapajus sp. (capuchin monkeys). Therefore, these data support the notion that Alouatta sp. is highly susceptible to infection and YFV-induced lesions, whereas Callithrix sp. is susceptible to infection but has a lower frequency of YFV-induced lesions.

Evaluation of pathogenicity of Salmonella Gallinarum strains harbouring deletions in genes whose orthologues are conserved pseudogenes in S. Pullorum.

The diseases caused by Salmonella Gallinarum and S. Pullorum in chickens known as fowl typhoid and pullorum disease, respectively, pose a great threat to the poultry industry mainly in developing countries, since they have already been controlled in the developed ones. These bacteria are very similar at the genomic level but develop distinct host-pathogen relationships with chickens. Therefore, a deep understanding of the molecular mechanisms whereby S. Gallinarum and S. Pullorum interact with the host could lead to the development of new approaches to control and, perhaps, eradicate both diseases from the chicken flocks worldwide. Based on our previous study, it was hypothesised that metabolism-related pseudogenes, fixed in S. Pullorum genomes, could play a role in the distinct host-pathogen interaction with susceptible chickens. To test this idea, three genes (idnT, idnO and ccmH) of S. Gallinarum str. 287/91, which are pseudogenes on the S. Pullorum chromosomes, were inactivated by mutations. These genetically engineered strains grew well on the solid media without any colony morphology difference. In addition, similar growth curves were obtained by cultivation in M9 minimal medium containing D-gluconate as the sole carbon source. Infection of chickens with idnTO mutants led to increased numbers of bacteria in the livers and spleens at 5 days post-infection, but with slightly decreased heterophil infiltration in the spleens when compared to the wild-type strain. On the other hand, no significant phenotypic change was caused by mutation to ccmH genes. Apart from the above-mentioned alterations, all S. Gallinarum strains provoked similar infections, since mortality, clinical signs, macroscopic alterations and immune response were similar to the infected chickens. Therefore, according to the model applied to this study, mutation to the idnTO and ccmH genes showed minor impact on the fowl typhoid pathogenesis and so they may be relics from the ancestor genome. Our data hints at a more complex mechanism driving the distinct host-pathogen interaction of S. Gallinarum/Pullorum with chickens than differential inactivation of a few genes.

Gallic and ellagic acids: two natural immunomodulator compounds solve infection of macrophages by Leishmania major.

Leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from Leishmania genus. Conventional treatments are high costly, and promote a sort of side effects. Besides, protozoan resistance to treatments has been reported. Natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control parasitemia. Gallic acid (GA) and ellagic acid (EA) are plant-derived phenolic compounds which are able to induce antiinflammatory, gastroprotective, and anticarcinogenic activities. Therefore, the antileishmania, cytotoxic, and immunomodulatory activities of GA and EA were evaluated in this study. Both GA and EA were able to inhibit the growth of Leishmania major promastigotes (effective concentration (EC50) values 16.4 and 9.8 µg/mL, respectively). The cytotoxicity against BALB/c murine macrophages for GA and EA was also assessed (CC50 values 126.6 and 23.8 µg/mL, respectively). Interestingly, GA and EA also significantly reduced the infection and infectivity of macrophages infected by L. major (EC50 values 5.0 and 0.9 µg/mL, respectively), with selectivity index higher than 20. Furthermore, both GA and EA induced high immunomodulatory activity evidenced by the increase of phagocytic capability, lysosomal volume, nitrite release, and intracellular calcium [Ca2+i] in macrophages. Further investigations are reinforced in order to evaluate the therapeutic effects of GA and EA in in vivo experimental infection model of leishmaniasis.