Table of Contents

Volume 1, Issue 2

  March/April 2010

  Pages 57 - 109

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Crowd control: Bacillus anthracis and quorum sensing

Sean M. Rollins and Raymond Schuch
Pages 57 - 59
http://dx.doi.org/10.4161/viru.1.2.11051
Abstract | PDF

In 1965, Dr. Alexander Tomasz identified a critical component of the DNA uptake mechanism used by competent Streptococcus pneumoniae: the pneumococci secrete a polypeptide that induces the expression of proteins to allow foreign DNA to pass through the bacterium's cell wall. This hormone-like substance was the first of numerous "quorum-sensing" factors that have since been identified in many microbial processes.  Detailed insights into the molecular mechanisms of quorum-sensing are now emerging, owing largely to studies focusing on the ability of marine organisms like Vibrio fischeri and Vibrio harveyi to produce light at high cell densities.  The complexities of bioluminescence induction, and indeed that of an ever increasing group of other quorum-sensing phenotypes, show that such signaling pathways are not just an interesting phenomenon but rather represent a widespread mechanism by which bacterial populations can communicate, coordinate behavior and act in a cooperative manner in the environment.

Open Access Article

Risk based HIV retesting: Back to the same old challenges

Florence Momplaisir and Barbara Turner
Pages 60 - 61
http://dx.doi.org/10.4161/viru.1.2.11052
Abstract | PDF

An estimated 230,000 Americans are unaware that they have HIV infection.  As a result, these individuals have not benefited from treatment for HIV infection and they may continue to spread the disease.  In 2006, the Centers for Disease Control and Prevention (CDC) reported that 40% of adults aged 18-64 had been tested for HIV but only 10% had been tested within the last 12 months.  A national survey conducted by the CDC in 2000 found that only about one-quarter of primary care providers and emergency physicians reported routinely testing their patients for HIV.  To improve the performance of HIV testing, in 2006 the CDC issued recommendations that patients in all health care settings be offered universal, opt-out HIV testing. Since that time, several studies have demonstrated the feasibility of opt-out testing but barriers to implementation persist. Many states still require signed consent and counseling and other logistical challenges include: insufficient time, competing priorities, and inadequate reimbursement.  Therefore, universal HIV testing remains an unrealized goal.




RESEARCH PAPERS

Open Access Article

The use of nitric oxide releasing nanoparticles as a treatment against Acinetobacter baumannii in wound infections

Mircea Radu Mihu, Uriel Sandkovsky, George Han, Joel M. Friedman, Joshua D. Nosanchuk and Luis R. Martinez
Pages 62 - 67
http://dx.doi.org/10.4161/viru.1.2.10038
Abstract | PDF

Acinetobacter baumannii (Ab) is a frequent cause of hospital acquired pneumonia and recently has increased in incidence as the causative agent of severe disease in troops wounded in Afghanistan and Iraq. Ab clinical isolates are frequently extremely resistant to antimicrobials, significantly complicating our capacity to treat infections due to this pathogen. Hence, the development of innovative therapeutics targeting mechanisms to which the bacteria are unlikely to evolve resistance is urgently needed. We examined the capacity of a nitric oxide -releasing nanoparticle (NO-np) to treat wounds infected with Ab. We found that the NO-nps were therapeutic in an experimental Ab murine wound model. Treatment with NO-nps significantly accelerated healing of infected wounds. Histological study demonstrated that NO-np treatment reduced suppurative inflammation, decreased microbial burden, and reduced the degradation of collagen. Furthermore, NO-np treatment alters the local cytokine milieu. In sum, we demonstrated that the NO-nps are an easily administered topical antimicrobial for the treatment of Ab wound infections, and our findings suggest that NO-nps may also be ideal for use in combat or disaster situations.


Open Access Article

Frequent HIV testing among participants of a routine HIV testing program

Hazel Williams-Roberts, Yuchiao Chang, Elena Losina, Kenneth A. Freedberg and Rochelle P. Walensky
Pages 68 - 71
http://dx.doi.org/10.4161/viru.1.2.10570
Abstract | PDF

Massachusetts developed a routine HIV testing program in four sites from January–September 2002. Of the 2,502 patients tested, 453 (18.1%) reported ≥2 HIV tests within the prior three years. In multivariate analyses, frequent HIV testing was associated with younger age (18–30 years, OR = 1.42), a history of injection drug use (OR = 6.35), and men who had sex with men (OR = 3.49). Participants who reported multiple sexual partners (OR = 2.17) and high risk sexual behavior (OR = 2.02) were significantly more likely to have had a prior HIV test. Patients whose HIV risk was unknown had the highest association with frequent testing (OR = 13.18). Because characteristics of frequent HIV testers may inform behavioral interventions, there is a need to understand the motivation for repeatedly accessing HIV testing services.

Open Access Article

Role of luxS in Bacillus anthracis growth and virulence factor expression

Marcus B. Jones, Scott N. Peterson, Rosslyn Benn, John C. Braisted, Behnam Jarrahi, Kenneth Shatzkes, Dacheng Ren, Thomas K. Wood and Martin J. Blaser
Pages 72 - 83
http://dx.doi.org/10.4161/viru.1.2.10752
Abstract | PDF

Quorum-sensing (QS), the regulation of bacterial gene expression in response to changes in cell density, involves pathways that synthesize signaling molecules (auto-inducers). The luxS/AI-2-mediated QS system has been identified in both Gram-positive and Gram-negative bacteria. Bacillus anthracis, the etiological agent of anthrax, possesses genes involved in luxS/AI-2-mediated QS, and deletion of luxS in B. anthracis Sterne strain 34F₂ results in inhibition of AI-2 synthesis and a growth defect. In the present study, we created a ΔluxS B. anthracis strain complemented in trans by insertion of a cassette, including luxS and a gene encoding erythromycin resistance, into the truncated plcR regulator locus. The complemented ΔluxS strain has restored AI-2 synthesis and wild-type growth. A B. anthracis microarray study revealed consistent differential gene expression between the wild-type and ΔluxS strain, including downregulation of the B. anthracis S-layer protein gene EA1 and pXO1 virulence genes. These data indicate that B. anthracis may use luxS/AI-2-mediated QS to regulate growth, density-dependent gene expression and virulence factor expression.




ARTICLE ADDENDA

Open Access Article

Schistosoma haematobium and bladder cancer: What lies beneath?

Monica Catarina Botelho, Jose Carlos Machado and Jose Manuel Correia da Costa
Pages 84 - 87
http://dx.doi.org/10.4161/viru.1.2.10487
Abstract | PDF

Schistosoma haematobium is a parasitic flatworm that infects millions of people, mostly in the developing world, and is associated with high incidence of bladder cancer although why is not clear. But our group was able to define the mechanistic relationship for the first time between infection of S. haematobium and cancer. We used in vitro models to demonstrate the presence of informative carcinogenesis-associated phenotypes in CHO cells exposed to Sh total antigen, in which we showed increased cell proliferation, decreased apoptosis, up regulation of the anti-apoptotic molecule Bcl-2, down regulation of the tumor suppressor protein p27, and increased cell migration and invasion. We further discuss the molecular and cellular events that might be responsible for schistosomiasis-related bladder cancer.

Open Access Article

Guidance of antibiotic therapy with procalcitonin in lower respiratory tract infections: Insights into the ProHOSP study

Philipp Schuetz, Mirjam Christ-Crain, Werner Albrich, Werner Zimmerli and Beat Mueller
Pages 88 - 92
http://dx.doi.org/10.4161/viru.1.2.10488
Abstract | PDF

In the recently published ProHOSP trial, we investigated the safety and external validity of procalcitonin (PCT) guidance for antibiotic therapy in patients with different severities of lower respiratory tract infections, mainly pneumonia. In this addendum, we aim to extend the initial report by reinforcing the rational of the PCT algorithm and by presenting more detailed data on antibiotic therapy in different severities of infection. In milder, mostly viral respiratory infections (i.e. acute or chronic bronchitis) initial prescription of antibiotics was markedly reduced by PCT guidance because PCT remained low in most patients. In pneumonia, PCT showed a severity-dependent increase and highest levels in patients with positive blood cultures. Thus, the main effect in pneumonia was a severity- and bacteremia-adapted reduction of the duration of antibiotic courses. In lower respiratory tract infections, PCT guidance had a differential effect on antibiotic exposure depending on the underlying type and severity of respiratory tract infection.

Open Access Article

Mapping the selection mechanisms by bacterial GEFs

Zhi Huang and Jijie Chai
Pages 93 - 96
http://dx.doi.org/10.4161/viru.1.2.10617
Abstract | PDF

Mimicry of eukaryotic signaling enzymes is a common strategy used by bacterial pathogens to manipulate host cellular signaling. The E. coli type III effector protein Map belongs to a large family of bacterial virulence factors that activate host Rho GTPase signaling pathways through an unknown molecular mechanism. Our recent structural study, coupled with biochemical and functional assays, establishes that this family protein, including Map, IpgB1/2 and SifA/B secreted by E. coli, Shigella, and Salmonella respectively, acts as functional mimic of mammalian guanine nucleotide exchange factors (GEFs). Furthermore, we show that Map and its family members share a conserved mechanism with human Dbl GEFs for selection of various GTPase isoforms，revealing an evolutionary dynamic state of protein mimicry.

Open Access Article

Clostridium perfringens type C isolates rapidly upregulate their toxin production upon contact with host cells: New insights into virulence?

Bruce McClane
Pages 97 - 100
http://dx.doi.org/10.4161/viru.1.2.10679
Abstract | PDF

Since tetanus was first described by Hippocrates, the devastating diseases caused by pathogenic members of the Gram-positive, anaerobic sporeforming genus Clostridium have ranked among the most dreaded afflictions of humans and domestic animals. The quintessential hallmark of all clostridial diseases is the involvement of potent protein toxins. However, except for some foodborne botulism cases, clostridial diseases are not intoxications involving preformed toxins; rather, these illnesses are true infections involving toxin production by bacteria growing inside the host.

Open Access Article

Transmissible encephalopathy agents: Virulence, geography and clockwork

Laura Manuelidis
Pages 101 - 104
http://dx.doi.org/10.4161/viru.1.2.10822
Abstract | PDF

Transmissible spongiform encephalopathies (TSEs) are caused by infectious agents with stable virulence characteristics that are not encoded by the host. Agent-specific features of virulence include variable disease latency and tissue pathology in a given host, as well as the ability to spread to many species. Such cross-species infections contradict predictions based on the prion hypothesis. Recent transmissions of several human agents to normal mice and to monotypic neural cells in culture, underscore the existence of unique agent clades that are prevalent in particular geographic regions. Examples include the epidemic UK bovine agent (BSE) and the New Guinea kuru agent. The virus-like biology of unique TSE agents, including epidemic spread, mutation, and superinfection, can be used to systematically define features of virulence that distinguish common endemic from newly emerging strains.

Open Access Article

Significance of reduced reactivity in ELISPOT assay to RD antigens of Mycobacterium tuberculosis in BCG vaccinated individuals exposed to a patient with tuberculosis

Michael Eisenhut
Pages 105 - 106
http://dx.doi.org/10.4161/viru.1.2.11054
Abstract | PDF

Children with previous BCG immunization, who were investigated for mycobacterium tuberculosis infection during an outbreak of tuberculosis, were found to have a reduced reactivity in a gamma interferon release assay for mycobacterium tuberculosis. This may represent reduced presence of mycobacterium tuberculosis in BCG vaccinated individuals, who eliminated infection due to enhancement of the immune response by immunization. Alternatively bacterial load may have been suppressed below detection threshold of the body's immune system. Future research needs to develop methods of direct and specific detection of low bacterial loads of mycobacterium tuberculosis in vivo. One method worth further development is radio-immuno-szintigraphy, which has been successful in detection of mycobacterium tuberculosis in vivo in animal studies.

Open Access Article

Relevance of serology and molecular methods for detection of Hepatitis B virus in Egyptian children with hematological malignancy

Maysaa El Sayed Zaki and Rasha Abd El Malak
Pages 107 - 109
http://dx.doi.org/10.4161/viru.1.2.10618
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