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PubMed1977

[Utilization of inorganic sulfur sources by Staphylococcus aureus strains].

Staphylococcus aureus strains of different host-adapted variants (Meyer 1966) have been tested for their ability to use inorganic sulfur sources. All the 25 strains tested were able to utilize sodium sulfide as sulfur source in a medium similar to that described by Kloos and Pattee (1965). Using S. aureus strain 116/74 grown in a medium containing Na2-35S as the only sulfur source we studied incorporation and insertion of inorganic sulfide into sulfur containing amino acids. In disintegrated and fractionated cellular material we could find 35S labelled homocystine and methionine as major compounds, and cystine, cysteic acid, homocysteic acid, and beta-sulphopyruvate as minor compounds. The occurrence of homocystine and the sulfonic acids in bacterial proteins is rather uncommon.

Bacterial Proteins↗
PubMed2001

How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A.

Interferons (IFNs) induce an antiviral state in the cell through complex and indirect mechanisms, which culminate in a direct inhibition of viral replication and stimulation of the host adaptive responses. Viruses often counteract with elaborate strategies to interfere with the induction as well as action of IFN effector molecules. This evolutionary battle between viruses and IFN components is a subject of intense research aimed at understanding the immunopathogenesis of viruses and the molecular basis of IFN signaling and action. In the case with hepatitis C virus (HCV), this may have profound implications for the therapeutic use of recombinant IFN in treating chronic hepatitis C. Depending on the subtype of HCV, current IFN-based treatment regimens are effective for only a small subset of chronic hepatitis C patients. Thus, one of the Holy Grails in HCV research is to understand the mechanisms by which the virus may evade IFN antiviral surveillance and establish persistent infection, which may eventually provide insights into new avenues for better antiviral therapy. Despite the lack of an efficient tissue culture system and an appropriate animal model for HCV infection, several mechanisms have been proposed based on clinical studies and in vitro experiments. This minireview focuses on the HCV NS5A nonstructural protein, which is implicated in playing a role in HCV tolerance to IFN treatment, possibly in part through its ability to inhibit the cellular IFN-induced PKR protein kinase.

Animals↗
PubMed1999

Edema disease as a model for systemic disease induced by Shiga toxin-producing E. coli.

Edema disease (ED) is a naturally occurring disease of weaned pigs caused by host adapted strains of E. coli that produce Shiga toxin (STEC). We determined the temporal and quantitative relationships between intestinal colonization by STEC, levels of Shiga toxin (Stx2e) in the gut, in the blood, and clinical manifestations of ED. Bacterial colonization (10(8) CFU/cm ileum) was highest 4 days post inoculation (pi) in animals that did not develop clinical disease and 6 days pi in animals with clinical signs of ED. The mean time for the development of clinical signs of ED was 6 days pi (range 4-10). Average peak titers of Stx2e in the ileum were 1:16,384 in asymptomatic animals and 1:32,768 in clinical animals. Titers of Stx2e in the feces reflected the toxin titers in the ileum but were lower. Intestinal titers of Stx2e and the density of bacterial colonization were predictive of clinical ED for a group of animals but not for individuals. Approximately 50% of the pigs that had Stx2e titers of > or = 1:4096 and a bacterial density of > or = 10(6) CFU/cm in their ileum, had clinical ED. Pigs that had intestinal Stx2e titers < 1:4096 were asymptomatic. Stx2e was detected in the red cell fraction of blood from some of the pigs with clinical ED and in some that were asymptomatic. Stx2e was not detected in the serum of any animals. ED may be a useful model for predicting the temporal and quantitative relationships between bacterial colonization, Stx levels in the gut and blood and systemic disease for STEC in other species.

Animals↗
PubMed2002

Host recognition by pathogenic fungi through plant flavonoids.

A common characteristic among fungal pathogens of plants is that each specializes on a narrow range of specific plants as hosts. One adaptation to a specific host plant is the recognition of the host's chemicals which can be used to trigger genes or developmental pathways needed for pathogenesis. The production of characteristic flavonoids by plants, particularly those exuded from roots by legumes, appear to be used as signals for various microbes, including symbionts as well as pathogens. Nectria haematococca MPVI (anamorph: Fusarium solani) is a soil-borne pathogen of garden pea (Pisum sativum) which serves as a useful model in studying host flavonoid recognition. This fungus displays flavonoid induction of specific pathogenicity genes as well as stimulation of development needed for pathogenesis. Here, we summarize the study of flavonoid-inducible signal pathways which regulate these trait, through identification of transcription factors and regulatory components which control these responses. The characterization of the components a pathogen uses to specifically recognize its host provides insights into the host adaptation process at the molecular level.

Adaptation, Physiological↗
PubMed1995

An immunocytochemistry study comparing the occurrence of neuroactive substances in the nervous system of cercariae and metacercariae of the eye fluke Diplostomum spathaceum.

The nervous system of two larval stages (cercariae, metacercariae) of eye fluke Diplostomum spathaceum was investigated immunocytochemically by the application of antisera to the amino acid glutamate and to neuropeptides isolated from invertebrates (Mollusca) and from vertebrates to whole-mount preparations. In cercariae, positive immunoreactivity (IR) was observed with antisera raised against Catch-relaxing peptide (CARP), FMRFamide, alpha-caudodorsal cell peptide (alpha-CDCP), substance P, vasotocin, and vasopressin. In metacercariae, in addition to positive staining with these antisera, the ones raised against glutamate, APGWamide, caudodorsal cell hormone I (CDCH-I), and small cardiac peptide B (SCPB) also gave positive IR in the nervous system. In the two larval stages the most extensive pattern of IR was observed with anti-FMRFamide and anti-CARP. In the nervous system of metacercariae the same immunoreactive neurosubstances appeared to be present as in that of cercariae. The increase in the variety of immunoreactive neurosubstances in the more complex nervous system of metacercariae is discussed in relation to parasite development and to host adaptation.

Animals↗
PubMed2005

[Special features of the skin in newborns and young infants].

Detailed knowledge of the special features of neonatal and infant skin is a prerequisite for adequate skin care in this age group. Immediately postpartum, the newborn baby's skin assumes vital functions regarding water and electrolyte homeostasis and thermoregulation, as well as innate and adaptive host defense. Due to its functional and structural immaturity, premature skin requires special care. Mature neonates demonstrate benign, transient skin lesions that do not require specific therapy but have to be distinguished from serious and potentially life-threatening illnesses.

Humans↗
PubMed2004

Identification of Cryptosporidium isolates from cockatiels by direct sequencing of the PCR-amplified small subunit ribosomal RNA gene.

Cryptosporidium is a significant pathogen in humans and animals. Cases of infection by C. meleagridis or C. baileyi with zoonotic potential have also been reported in domestic birds; and recent studies indicate the presence of new host-adapted species or genotype in birds. Therefore, accurately identifying isolates is important for understanding the epizootiology of Cryptosporidium infection in birds and for the control of human cryptosporidiosis. Cryptosporidium has been detected in cockatiels, but the species or genotype of isolates remains unclear because identification was performed using conventional microscopy. We report herein the species or genotype of isolates from two cockatiels distinguished by a PCR-based diagnostic method. The isolates were found to be C. meleagridis and C. baileyi, respectively. This study documents the first discovery of C. meleagridis and C. baileyi in cockatiels and suggests that pet birds may play an important role in the epidemiology of cryptosporidiosis.

Animals↗
PubMed2005

Genetic characterization of H5N1 avian influenza viruses isolated in southern China during the 2003-04 avian influenza outbreaks.

The recent H5N1 avian influenza outbreaks in Asia spread over more than 8 countries. It has caused enormous economic loss and grand challenges for the public health. During these breakouts we isolated three strains of H5N1 Avian Influenza Virus (AIV) from chickens and one from duck in different farms of Southern China. We completely sequenced these four AIVs. Molecular characterization demonstrated that these strains retain the reported H5N1 AIV sequence properties relevant to virus virulence and host adaptation. Phylogeny results demonstrated that three of these isolates (except A/Chicken/Guangdong/174/04) were closely linked to other H5N1 AIVs isolated from the recent H5N1 outbreaks in Asia. Six of 8 segments (except PA and M) of A/Chicken/Guangdong/174/04 also shares a close linkage to other H5N1 AIVs isolated from the recent H5N1 outbreaks. However, the PA gene of A/Chicken/Guangdong/174/04 and another H5N1 strain forms a distinct subgroup along with an H6N1 AIV, and the M gene of A/Chicken/Guangdong/174/04 shows a close linkage to some H5N1 AIVs from aquatic species in China. Our findings suggest that a new genotype of AIV (in addition to previous reported ones) was present during the 2003-04 Asian bird flu outbreaks and that continuing virus surveillance of AIVs be conducted to monitor the evolutionary paths of the A/Chicken/Guangdong/174/04-like AIVs.

Animals↗
PubMed1983

Growth pattern of tumor xenografts in Wistar rats after treatment with cyclophosphamide, total lymphoid irradiation and/or cyclosporin A.

Wistar rats treated with cyclophosphamide, total lymphoid irradiation (TLI), and/or cyclosporin A (CSA) develop a state of immune suppression permitting the growth of tumor xenografts. Experiments were carried out on this newly developed model to investigate the growth patterns of a mouse osteosarcoma and a human colon adenocarcinoma. The combination of cyclophosphamide and CSA permitted a limited period of growth of the mouse osteosarcoma with a tumor take rate of 66%. No takes were observed with the human adenocarcinoma. The combination of cyclophosphamide and TLI resulted in a period of immunosuppression followed by recovery of the immune status. During the period of immunosuppression, tumor xenografts showed a 100% take rate. The most efficient immunosuppression was achieved by a combination of cyclophosphamide, TLI and CSA administered on alternate days. Wistar rats subjected to this treatment showed prolonged tolerance to mouse osteosarcoma and human adenocarcinoma xenografts. There was no alteration in the tumor doubling time or histological morphology of the xenografts in the adapted host as compared with those in the donor tumors. The tumor growth curve showed a pattern of initial growth, a period of stagnation, followed by a steady but slower growth phase. The significance of the results and the advantages of the rat model described in this paper for human tumor xenotransplantation are discussed.

Adenocarcinoma↗
PubMed1994

Genomic lineage of Salmonella enterica serovar Dublin.

Thirty five strains of the host adapted Salmonella serotype Dublin (S. Dublin) have been characterized by IS200 patterns, ribotyping, pulsed-field gel electrophoresis (PFGE), restriction fragment polymorphism after hybridization with five randomly cloned DNA-fragments of S. enteritidis (RFLP), and plasmid profiling in order to divide the strains into 'genomic lines'. For comparison, 20 other strains of 9 different group-D serotypes were included. The IS200 patterns were identical in all strains of S. Dublin examined. These patterns were different from those observed in other group-D Salmonella with the exception of one strain S. Enteritidis phage type 11 and a strain of S. Rostock. The insertion element IS200 was not detected in strains of S. Dar-es-Salam, S. (II) 9,12:z:-, and S. Panama. RFLP, based on probing with five random cloned chromosomal fragments gave the same pattern in all strains except for one isolate from the UK. This strain was also found to have an unique PFGE pattern and ribotype. Among the remaining strains, three different PFGE patterns and 7 different ribotypes were observed. Based on all four typing methods, 8 different 'genomic lines' of S. Dublin were identified. The same grouping could be obtained from the use of ribotyping alone, but PFGE and RFLP were found to provide valuable information on possible relationships between ribotypes. Seven different plasmid profiles and a group of strains without plasmids were observed. In several cases, the same plasmid profile was shown to be present in more than one 'genomic line'.

Bacterial Typing Techniques↗
PubMed1989

Induced frameshifting mechanism of replication for an information-carrying scrapie prion.

A specific mistranslation mechanism for the replication of an infectious protein is described. The feedback mechanism requires the infectious agent to induce concerted frameshifts during the translation of a cellular gene. Each module of the tandem repeat region of the gene encoding the prion protein (PrP) associated with scrapie infectivity contains multiple sites of potential ribosomal frameshifting. It is proposed that some aberrant variants of PrP containing frameshifted peptides within the octapeptide repeat region of the protein backbone are able to replicate and cause scrapie by interfering with the translation and simultaneous translocation of nascent PrP molecules into the lumen of the endoplasmic reticulum. The model provides a plausible explanation for the behaviour of host-adapted scrapie strains as well as the aetiology of scrapie-like diseases. The hypothesis that a mistranslated PrP is the scrapie agent can also explain discrepancies between the published amino acid sequence of PrP and the sequence deduced from the gene.

Amino Acid Sequence↗
PubMed2006

Antibacterial drug discovery--then, now and the genomics future.

Drug discovery research in the area of infectious diseases, in particular that dealing with antibacterial/antibiotic susceptibility and resistance, is in a process of continuing evolution. Steeped in the history of the highly successful intervention with chemotherapeutic agents to treat human infections, the emergence of drug-resistant pathogens worldwide presents a serious unmet medical need, if not a pending catastrophe. Research in both academia and industry over the past 30 years using molecular biology, genetics and more recently--bacterial genomics--has assembled key enabling technologies to increase productivity and success rates in the discovery and development of novel antibacterial agents. However genomics is not limited only to antibacterial target selection but provides the opportunity to further understand key interactions in the use of antibacterial compounds as therapeutic agents (such as resistance emergence, susceptibility, efflux, interactions between compound and pathogen, etc.). Genomics also offers the potential for insights into: bacterial niche adaptation, host susceptibility, treatment regimens, antibiotic resistance, pharmacokinetics (e.g., host metabolism differences), safety and the microbial genesis of chronic diseases (e.g., gastric ulceration).

Anti-Bacterial Agents↗
PubMed2026

Phylogenomic and Clinical Perspectives of an East Asia-Specific Cluster of Mycobacterium massiliense.

BACKGROUND: Mycobacterium abscessus subspecies massiliense (MAM) can form genetically related clusters through continuous within-host adaptations. RESEARCH QUESTION: What is the epidemiologic and clinical significance of the sequence type 120 (ST120) strain of MAM, an East Asia-specific cluster? STUDY DESIGN AND METHODS: Isolates were obtained from patients with MAM pulmonary disease at Seoul National University Hospital between October 1, 2019, and December 31, 2023. These isolates were analyzed using multilocus sequence typing and colony morphotyping and were evaluated for glycopeptidolipid biosynthesis-related gene deletions. Whole-genome sequencing was performed for phylogenomic and pangenome analyses, incorporating MAM genome data from public databases. Finally, the clinical course and treatment outcomes of patients infected with ST120 were evaluated. RESULTS: Among the isolates obtained from 136 patients, 50 isolates (36.8%) were classified as ST120. All ST120 isolates exhibited a rough colony morphotype and harbored deletions in glycopeptidolipid biosynthesis-related genes. From 796 global strains, ST120 was identified exclusively in the isolates obtained from South Korea (51/137 isolates [37.1%]), Japan (3/53 [5.7%]), and Taiwan (2/52 [3.8%]). Genomic analysis revealed the stepwise genetic evolution of ST120, suggesting transmission from Taiwan to Japan and from Japan to South Korea. The ST120 strains exhibited genetic mutations associated with virulence and structural alterations within the ESX system. Consequently, patients with ST120 strain infections had a higher prevalence of cavitary disease (23/50 [46%]) than those infected with non-ST120 strains (19/86 [22.1%]; P = .004). Among those who initiated treatment, the proportion of microbiological cure was lower in patients with ST120 infection (6/15 [40.0%]) than in those with non-ST120 infection (24/34 [70.6%]; P = .043). INTERPRETATION: Our results show that ST120, a strain predominantly found in South Korea, is characterized by the extensive loss of glycopeptidolipid biosynthesis-related genes and is associated with increased disease severity and worse treatment outcomes.

Humans↗
PubMed2026

Temporal Patterns in the Occurrence of Principal Salmonella Serotypes for Raw Meat and Poultry Products in the United States: 1998-2024.

Microbial foodborne pathogens, such as Salmonella, have the characteristic that only some subgroups of these bacteria are highly pathogenic to humans. For the Salmonella species enterica, there are more than 2,600 serotypes. These serotypes can be host-adapted so that for any animal reservoir, such as a particular food animal species, fewer than 10 serotypes make up more than fifty percent of isolates found in the reservoir. The highly concentrated nature of serotypes within a reservoir is a key to the findings of many studies and the cornerstone of some food safety programs. Nevertheless, a key limitation is that the dominant serotypes for a reservoir are likely to change over time. This is problematic because the risk of illness associated with a reservoir can increase dramatically if a more pathogenic serotype replaces one or more less pathogenic serotypes, and vice versa. In the United States, meat and poultry have been sampled continuously by the United States Department of Agriculture Food Safety and Inspection Service (USDA FSIS) for nearly 30&#xa0;years. For this study, these data are used to describe how the occurrence of the most common serotypes for each sampled commodity has changed over time. Insight into how often and how rapidly the most common serotypes change is important for designing effective mitigation strategies. To aid the development of such a mitigation strategy, we developed a classification system to categorize serotypes based on the direction and magnitude of change in each serotype over time. This information is combined with a ranking system that describes the relative virulence of each serotype using genomic and epidemiological virulence patterns. We then developed a heuristic system to support risk management decisions regarding the potential risks and benefits of applying serotype-specific interventions.

Compositional data↗
PubMed2004

Eimeria tenella sporozoites and merozoites differentially express glycosylphosphatidylinositol-anchored variant surface proteins.

Little is known about glycosylphosphatidylinositol (GPI)-linked surface proteins in the coccidian parasite Eimeria tenella. Examination of 28,550 EST sequences from the sporozoite and second merozoite developmental stages of the parasite led to the identification of 37 potential GPI-linked variant surface proteins, termed EtSAGs. Analysis of the complete nucleotide sequences of 23 EtSAG genes separated them into two multi-gene families. All the predicted EtSAG proteins (which vary in length from 228 to 271 residues) have an N-terminal hydrophobic signal peptide, a C-terminal hydrophobic GPI signal-anchor peptide and an extracellular domain organised around six cysteine residues, the positions of which are conserved within each family. Using specific antibodies against a small number of recombinant-expressed EtSAGs, the surface localisation and GPI-anchorage of members of both families was confirmed experimentally. Expression of EtSAGs is differentially regulated between the oocyst/sporozoite and second generation merozoite stages, with only one expressed specifically in the sporozoite, a small number expressed in both stages and the majority expressed specifically in the second generation merozoite. Preliminary data support a model in which multiple variant surface antigens are co-expressed on individual parasites, rather than a model of antigenic switching. The biological role(s) of EtSAGs and the effect(s) that expression of a complex repertoire of variant surface antigens by the second generation merozoite has on host adapted immunity are unknown.

Amino Acid Sequence↗
PubMed2006

Intraspecific variability of Pythium myriotylum isolated from cocoyam and other host crops.

Intraspecific variability within 51 isolates of Pythium myriotylum from cocoyam (Xanthosoma sagittifolium) and other host crops was analysed using optimum growth temperature, esterase banding patterns, AFLPs, rDNA-ITS sequencing, and virulence to cocoyam. P. myriotylum isolates virulent to cocoyam could easily be differentiated from other isolates of P. myriotylum by their optimum growth temperature. Isolates from cocoyam grew best at 28 degrees C with no growth at 37 degrees C, while P. myriotylum isolates from other host crops had their optimum growth temperature at 37 degrees C. Esterases produced consistent zymograms with 18 discrete esterase markers, but no monomorphic markers were produced for isolates virulent to cocoyam. Isozyme profiles based on esterase analysis showed that isolates that infect cocoyam plantlets formed a related group, irrespective of their geographic origin. P. myriotylum isolates from other host plants also grouped together, but could clearly be distinguished from the cocoyam cluster. AFLPs produced 189 scorable bands for the cocoyam isolates, of which 77% are monomorphic. Phenetic analysis of AFLP data grouped all isolates originating from cocoyam together except for the isolates C103-04, CMR17, CMR22, and CMR25. These isolates regrouped with isolates of Pythium myriotylum from other host crops or the outgroup and were found not to be pathogenic for cocoyam. ITS sequences of isolates of P. myriotylum from cocoyam were 99.1-99.7% identical to sequences deposited in GenBank. However, alignments of ITS sequences revealed a base transition at position 824 from adenine in typical isolates of P. myriotylum to guanine in isolates that could infect cocoyam plantlets. In a limited pathogenicity test, all isolates from cocoyam having guanine at position 824 were able to infect tissue culture derived cocoyam but not those exhibiting adenine. This study demonstrates for the first time, molecular evidence that isolates of P. myriotylum that infect cocoyam are distinct from P. myriotylum isolates from other crops and have developed a certain degree of host adaptation.

Crops, Agricultural↗
PubMed2005

Effective sizes of macroparasite populations: a conceptual model.

Effective population size (N(e)) is a crucial parameter in evolutionary biology because it controls genetic drift and the response to selection. Thus, N(e) influences evolutionary processes in parasites, such as speciation, host-race formation, local host adaptation and the evolution of drug resistance. However, N(e) is a parameter that is ignored almost completely in parasitology. Our goal is to provide a conceptual framework that facilitates future studies of the N(e) of macroparasites. The key feature of macroparasite populations is that breeders are subdivided into infrapopulations. We use a model of subdivided breeders to show how some basic demographic factors that control N(e) in all species could be estimated for macroparasites. An important conclusion is that several features of parasite life cycles probably function in concert to reduce N(e) below that expected in a single free-living population of equivalent census size.

Animals↗
PubMed2006

BCG vaccine elicits both T-cell mediated and humoral immune responses directed against mycobacterial lipid components.

The universe of antigens recognized by alphabeta T cells has recently been expanded to include not only major histocompatibility complex (MHC)-presented protein antigens but also CD1-presented lipid antigens. The significance of lipid-reactive T cells in host defense has been appreciated, using the guinea pig model of human tuberculosis. Here, we show that immunization with Mycobacterium bovis bacillus Calmette-Guerin (BCG), the commonly used anti-tuberculosis vaccine, induces activation of guinea pig cytotoxic T cells recognizing BCG lipids in the context of CD1 molecules. Further, BCG-immunized, but not mock-immunized, guinea pigs mount IgG antibody responses directed against lipoarabinomannnan, an essential cell wall lipid component of mycobacteria. These observations emphasize the ability of BCG to activate the host adaptive immunity to mycobacteria-derived lipids, which could potentially contribute to protection against tuberculosis.

Animals↗