MicrobiologyBytes

Chagas disease is considered the largest parasitic disease burden in Latin America with a cost of the loss of 667,000 Disability Adjusted Life Years in 2002. Trypanosoma cruzi, the parasite that causes Chagas disease, infects approximately 9.8 million people in the Americas with 200,000 new Chagas cases annually. Most transmission occurs by contamination with the parasite-containing faeces of triatomine insect vectors (“kissing bugs”). There is no vaccine available and treatment shows limited effectiveness, comes with troublesome side effects, and is out of reach of most people in endemic countries. Therefore, as with most parasitic infections, control of transmission by the vectors is the control strategy of choice.

Pesticide spraying has effectively halted transmission in most of southern South America, especially where the bugs live exclusively inside houses. In Mesoamerica, bugs living in the forest readily reinfest treated houses. In addition, one of the main species of insect that transmits Chagas in Mesoamerica, Triatoma dimidiata, although it looks similar in different localities, may consist of genetically distinct populations, even different species, which differ in how efficiently they transmit the parasite: characteristics which confound control efforts. Nuclear and mitochondrial DNA were analyzed to characterize different populations of T. dimidiata from Mexico and Central America. Both the nuclear and mitochondrial DNA show that there is a very distinct population of T. dimidiata, perhaps even a different species, that lives in very close proximity with other T. dimidiata in Mexico and Guatemala. The nuclear DNA divides the remaining T. dimidiata into three additional genetically distinct groups. However, the mitochondrial DNA does not distinguish these additional groups. This study helps inform control efforts by showing where genetically distinct populations of T. dimidiata occur.

Since 1997, the Central America Initiative for the Control of Chagas disease has shown dramatically different results following insecticide spraying in houses, e.g. in Nicaragua, the bugs did not return; in stark contrast to rapid reinfestation in Jutiapa, Guatemala. It is important to understand how much of the differences in epidemiology and control outcomes are due to distinct taxa of T. dimidiata. The area of Peten, Guatemala has not been included in the control program since most are forest populations. Deforestation and increasing encroachment of human populations in the area means that T. dimidiata could become domesticated in this region. It is critical to realize that there are at least two distinct T. dimidiata populations in this area (and in Mexico and Belize) as control measures are designed. For effective control it will be imperative to understand the mechanisms maintaining this reproductive isolation and the epidemiological importance of distinct taxa.

Two Distinct Triatoma dimidiata (Latreille, 1811) Taxa Are Found in Sympatry in Guatemala and Mexico. PLoS Negl Trop Dis 3(3): e393
Approximately 10 million people are infected with Trypanosoma cruzi, the causative agent of Chagas disease, which remains the most serious parasitic disease in the Americas. Most people are infected via triatomine vectors. Transmission has been largely halted in South America in areas with predominantly domestic vectors. However, one of the main Chagas vectors in Mesoamerica, Triatoma dimidiata, poses special challenges to control due to its diversity across its large geographic range (from Mexico into northern South America), and peridomestic and sylvatic populations that repopulate houses following pesticide treatment. Recent evidence suggests T. dimidiata may be a complex of species, perhaps including cryptic species; taxonomic ambiguity which confounds control. The nuclear sequence of the internal transcribed spacer 2 (ITS2) of the ribosomal DNA and the mitochondrial cytochrome b (mt cyt b) gene were used to analyze the taxonomy of T. dimidiata from southern Mexico throughout Central America. ITS2 sequence divides T. dimidiata into four taxa. The first three are found mostly localized to specific geographic regions with some overlap: (1) southern Mexico and Guatemala (Group 2); (2) Guatemala, Honduras, El Salvador, Nicaragua, and Costa Rica (Group 1A); (3) and Panama (Group 1B). We extend ITS2 Group 1A south into Costa Rica, Group 2 into southern Guatemala and show the first information on isolates in Belize, identifying Groups 2 and 3 in that country. The fourth group (Group 3), a potential cryptic species, is dispersed across parts of Mexico, Guatemala, and Belize. We show it exists in sympatry with other groups in Peten, Guatemala, and Yucatan, Mexico. Mitochondrial cyt b data supports this putative cryptic species in sympatry with others. However, unlike the clear distinction of the remaining groups by ITS2, the remaining groups are not separated by mt cyt b. This work contributes to an understanding of the taxonomy and population subdivision of T. dimidiata, essential for designing effective control strategies.

Related:

• Neglected Tropical Diseases in Latin America and the Caribbean

Kaposi’s sarcoma (KS) is a multifocal tumour only found in a few groups of people, including elderly Mediterranean men, individuals in Africa and patients with immune disorders. The tumours arise from the formation of new blood or lymphatic vessels (angiogenesis or lymphangiogenesis) due to the proliferation of endothelial cells. In 1994 Chang and Moore identified a new virus, Kaposi’s sarcoma-associated herpesvirus (KSHV) as the cause of these tumours.

Unlike other herpesviruses, the seroprevalence of KSHV is not ubiquitous, perhaps only 5% in those countries with low KSHV rates such as the USA and Northern Europe). Like all herpesviruses, KSHV infection persists for the life of the host and can enter either of two states: latency or lytic reactivation. In latency, the minimum number of viral genes is expressed to maintain the virus genome in dividing cells, evading immune detection. Lytic reactivation occurs when the virus re-enters productive replication to generate new progeny, lysing the host cell in the process. And like all herpesviruses KSHV likes to mess with the immune system of its host. The KSHV genome contains 86 genes, almost a quarter of which encode proteins with immunoregulatory activities such as T- and B-cell function, complement activation, the innate antiviral interferon response and natural killer cell activity. Many of these gene are homologues of cellular proteins.

• The KSHV proteins MIR1 and MIR2 ubiquitinate the cytoplasmic tail of MHC-I which triggers endocytosis and proteasomal degradation. This protects KSHV-infected cells from NK-mediated lysis. MIR2 can also down-regulate other components of the immune synapse, ICAM (CD54) and PECAM (CD31) by the same mechanism.
• The KSHV vOX2 protein causes the cellular CD200 receptor to deliver an inhibitory signal to granulocytes, although the mechanism by which this acts is not yet well defined.
• The KCP protein is present on the surface of KSHV virions and infected cells and protects them from complement attack by accelerating the decay of the classical pathway C3 convertase enzyme complex.
• The K15 protein activates MAP kinases and this affects immune function.
• KSHV encodes a family of 12 miRNAs. These regulate both B- and T-cell function.
• The K1 protein reduces the presence of B cell receptors on the surface of B cells and interferes with the production of cytokines, and inhibits apoptosis.
• The MIR2 protein down-regulates tetherin, which is involved in normal B-cell differentiation.
• Three KSHV chemokine homologues (vCCL1–3) have affinity for chemokine receptors (CCRs) and this affects T-cell responses.
• KSHV proteins inhibit interferon pathways.

Since KSHV infection results in lifelong persistence of the virus, these immunomodulation activities are clearly successful in preventing its elimination by the immune system. Many questions about KSHV infection remain unanswered, but we have learned valuable lessons about the normal function of the immune system through studying this virus.

Modulation of the immune system by Kaposi’s sarcoma-associated herpesvirus. Trends Microbiol. Feb 18 2009

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Related:

• MicrobiologyBytes: Human Herpesvirus 8 (HHV-8/KSHV)
• Cellular Genes Targeted by KSHV MicroRNAs
• Herpesviruses – not all bad?

Obesity is an enormous public health problem, arising as a consequence of alterations in eating behavior and how the body regulates energy intake, expenditure, and storage. Although an increased intake of energy-dense foods, especially when combined with reduced physical activity, contributes to the high prevalence of obesity, the existence of complex systems that regulate energy balance requires that this paradigm be considered in a larger context. In particular, recent evidence suggests that the gut microbiota may play a role in obesity by increasing the host’s energy-harvesting efficiency.

The treatment of obesity is challenging. Various surgical procedures designed to interfere with the ingestion and/or absorption of foods have been developed over the last 60 years. The Roux-en-Y gastric bypass (RYGB), currently the most commonly performed operation, involves creating a small gastric pouch from the stomach. This surgery leads to changes in acid exposure to the gastric remnant and proximal small bowel, restricts the amount and types of food that can be comfortably ingested, promotes a modest degree of nutrient malabsorption by shortening the length of the small bowel, and may result in intestinal dysmotility, all of which might be expected to alter the gut microbiota. Presently, very little is known about the changes in the gut microbiota that occur after RYGB, and no information has been published on changes in microbial diversity after RYGB in humans.

A recent study used the traditional Sanger and high-throughput 454 pyrosequencing methods to analyze the human gut microbiota in 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric bypass surgery. The goals were to identify specific microbial lineages that may play important roles in the development of obesity and also to determine whether the presence or abundance of these microorganisms changes after RYGB.

Human gut microbiota in obesity and after gastric bypass. PNAS USA January 21, 2009
Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the Bacteria in the human intestinal community were highly diverse, they fell mainly into 6 bacterial divisions that had distinct differences in the 3 study groups. Specifically, Firmicutes were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of Gammaproteobacteria. Numbers of the H2-producing Prevotellaceae were highly enriched in the obese individuals. Unlike the highly diverse Bacteria, the Archaea comprised mainly members of the order Methanobacteriales, which are H2-oxidizing methanogens. Using real-time PCR, we detected significantly higher numbers of H2-utilizing methanogenic Archaea in obese individuals than in normal-weight or post-gastric-bypass individuals. The coexistence of H2-producing bacteria with relatively high numbers of H2-utilizing methanogenic Archaea in the gastrointestinal tract of obese individuals leads to the hypothesis that interspecies H2 transfer between bacterial and archaeal species is an important mechanism for increasing energy uptake by the human large intestine in obese persons. The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion.

Related:

• Infectobesity: the bugs that make you fat
• Gut Feeling
• Antibiotics, your gut, and you
• Probiotics – weapons in the war against gut pathogens

Burkitt’s lymphoma (BL) was first described 50 years ago, and the first human tumour virus Epstein–Barr virus (EBV) was discovered in BL tumours soon after. Since then, the role of EBV in the development of BL has become more and more enigmatic. Only recently have we finally begun to understand, at the cellular and molecular levels, the complex and interesting interaction of EBV with B cells that creates a predisposition for the development of BL. This review discusses the intertwined histories of EBV and BL and their relationship to the cofactors in BL pathogenesis: malaria and the MYC translocation.

The curious case of the tumour virus: 50 years of Burkitt’s lymphoma. 2008 Nature Reviews Microbiology 6, 913-924

Related:

• DNA Viruses
• Viruses and Human Cancer
• Herpesvirus proteins that target key cellular processes
• Epstein-Barr Virus protein EBNA1 contributes to cancer
• Herpesviruses – not all bad?

There are many options still available for new antibiotics. While the search for new drugs seems to be declining, in this article in Microbiology Today, Flavia Marinelli takes a look at the need for new antimicrobials:

Novel classes of antibiotics are constantly required due to the expanding population of patients at risk and the growing prevalence of resistant pathogens in hospital- or community-acquired infections. Despite this need, major pharmaceutical players seem to be reducing their efforts to discover new antibiotics. This is due to a combination of factors such as the maturity, great competition and increased genericization of the antibiotic market. Unrealized expectations from high-throughput screening, combinatorial chemistry and pathogen-genome-derived targets have also had a negative effect. The perception prevails that the discovery of novel antibiotics is a very rare event. On the other hand, past and present successes speak for a return to microbial product screening.

Read more

Related:

• Streptomyces
• Antibiotics, your gut, and you
• Towards The Next 80 Years of Penicillin Production

Places to study at the University of Leicester are filling up fast:

Student application figures at the University of Leicester – named University of the Year for 2008-9 by the Times Higher – have rocketed. While applications nationally increased by over 7% – at Leicester applications are 16% higher than last year. That means that almost 20,000 students will chase 2,500 places at the University. Leicester has seen one of the largest increases in applications in the UK. In fact, over the past three years (2006-9) our applications have increased 49% – the 3rd biggest amongst traditional pre-1992 universities. This success is attributable to the strong research and teaching record Leicester enjoys and our very high student satisfaction record. Applications from Home and EU students for undergraduate study are up by 14% and overseas by 48%. Post graduate taught applications are also strong with an increase of 14% from home / EU students and 77% from overseas, an increase of 69% overall. Applications for postgraduate research are 37% higher than at the same point last year. In total, over 20,000 students study at the University of Leicester.

The good news is that in response to this, from 2010, you have not one but TWO choices to study microbiology at Leicester:

• Microbiology or:
• Medical Microbiology

A recent paper in Trends in Microbiology examined the possibilities for using bacteriophages in controlling biofilms which might result in healthcare-associated infections (Preventing biofilms of clinically relevant organisms using bacteriophage. 2009 Trends in Microbiology 17: 66-72). Biofilms are firmly attached microbial communities in which the organisms produce an extracellular polymeric matrix. Biofilm organisms might cause disease by detachment of individual cells or clumps of cells, by production of endotoxin, or by providing a niche for the development of antibiotic-resistant organisms. Biofilm organisms are usually tolerant to antimicrobial agents and the treatment of indwelling medical device-associated infections with systemic antimicrobial agents is usually ineffective.

Bacteriophages have been used for the treatment of infectious diseases in plants and animals, although few clinical trials with stringent negative controls have been carried out. There is a renewed interest in phage therapy in light of growing concerns with antimicrobial resistance in healthcare institutions worldwide. The use of phages for the treatment of device-associated infections could reduce the use of antibiotics and might limit the spread of resistant organisms.

There is some evidence for the potential of phages in biofilm control. Bacteriophage T4 phage was effective against E. coli biofilms in a glucose-limited chemostat, although the rate of phage synthesis and assembly were directly proportional to the amount of protein synthesis in the host cell. Some phages produce polysaccharide depolymerases that have the potential to degrade the biofilm matrix.

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However, there are several important characteristics of phage that should be considered when evaluating the potential of phages to control clinically relevant biofilms. The specificity of receptors for a single phage strain will determine its host range; some phage have specificity at the strain level, such as strain typing phages, whereas some are more broad-spectrum and can infect multiple strains or related species. This high degree of specificity could be a drawback, especially in the case of polymicrobial biofilms.

Few studies have explored the role of biofilms in the development of phage-resistance. Phage cocktails developed via the isolation of host range mutants and broad spectrum phage could be advantageous. Another important question is how a patient’s immune system will respond to the therapeutic introduction of phage. Phages are antigenic and elicit a response by serum antibodies and the cellular immune system. Repeated exposure to the phage results in increasing antibody titers and studies in animal models have shown that phage is cleared from the bloodstream by the cellular immune system. In a short-lived treatment, the antibody response to phage is weak except in cases were serum antibody titers are present before phage treatment. It is possible, although unproven, that phage might associate with biofilms and thereby be protected from inactivation. It might also be possible to design mutant phages with enhanced ability to resist clearance by the cellular immune system.

Related:

• Biofilms
• Saturday Cimema: Bacteriophage Therapy
• Bacteriophages for plant disease control
• Coevolution with viruses drives bacterial mutations