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Future Medicine

Publications in this journal

• Antigen detection as a point-of-care test for TB: the case of lipoarabinomannan.

  Authors: Soumya Swaminathan, Vv Banu Rekha

  Future microbiology. 7:559-64.

  Evaluation of: Lawn SD, Kerkhoff AD, Vogt M, Wood R. Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviralEvaluation of: Lawn SD, Kerkhoff AD, Vogt M, Wood R. Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study. Lancet Infect. Dis. 12(3), 201-209 (2011). The limitations of sputum smear microscopy, routine chest radiology for HIV-associated TB and culture-based diagnosis are well recognized, especially in resource-limited settings. The diagnostic accuracy of a new point-of-care lateral-flow urine strip test for lipoarabinomannan (Determine(®) TB-LAM; Alere, MA, USA), which costs US$3.50 per test strip and provides results within 30 min, was evaluated in a cohort of South African patients for HIV-associated TB before starting anti-retroviral therapy in South Africa. Prevalence of culture-positive TB cases was 17.4%, among which 28.2% had sputum smear positivity. Determine(®) TB-LAM (Alere, MA, USA) had highest sensitivity at low CD4 cell counts: 66.7, 51.7 and 39.0% at <50 cells, <100 cells and <200 cells per µl, respectively; specificity was greater than 98% for all strata. There was an incremental sensitivity when Determine TB-LAM was combined with smear microscopy, which did not differ statistically from the sensitivities obtained by testing a single sputum sample with the Xpert(®) MTB/RIF (Cepheid; CA, USA) assay. Determine TB-LAM is a simple, low-cost alternative to existing diagnostic assays for TB screening in HIV-infected patients with very low CD4(+) cell counts.

• Designing probiotics with respect to the native microbiome.

  Authors: Abolfazl Barzegari, Amir Ata Saei

  Future microbiology. 7:571-5.

  It is now well known that genetic and environmental factors affect the intestinal microbiome in an individual's lifetime and thus, different individuals possess different intestinal microbiomes andIt is now well known that genetic and environmental factors affect the intestinal microbiome in an individual's lifetime and thus, different individuals possess different intestinal microbiomes and microbial metabolomes. The intestinal microbiome has been shown to differ among individuals from the same sex, between sexes and between individuals of different ages. Different families and, from a larger perspective, different communities, possess different microbiomes, and thus corresponding metagenomes. Therefore, it can be deduced that each individual human being can be characterized by his/her own intestinal microbial fingerprint. This understanding may prove helpful in future individualized medicine. These microorganisms are natural beneficial symbionts of the GI tract, have adapted to their human host over million years of coevolution and are now regarded as the second human genome. The difference in intestinal microbiome of different populations may explain why the results from different clinical trials on probiotic efficacy do not match with each other. People pay much, but they benefit little. In this article, it is recommended to isolate probiotics from natives' microbiomes and in the interest of efficacy, to use them in the same population. This line of thought can be considered in future guidelines from the Food and Agriculture Organization and the WHO on evaluation of probiotics in foods.

• Diphtheria in Europe: current problems and new challenges.

  Authors: Katherina Zakikhany, Androulla Efstratiou

  Future microbiology. 7:595-607.

  Diphtheria, caused by toxigenic strains of Corynebacterium diphtheriae, is an ancient disease with high incidence and mortality that has always been characterized by epidemic waves of occurrence.Diphtheria, caused by toxigenic strains of Corynebacterium diphtheriae, is an ancient disease with high incidence and mortality that has always been characterized by epidemic waves of occurrence. Whilst towards the beginning of the 1980s, many European countries were progressing towards the elimination of diphtheria, an epidemic re-emergence of diphtheria in the Russian Federation and the Newly Independent States of the former Soviet Union demonstrated a continuous threat of the disease into the 1990s. At present, the epidemic is under control and only sporadic cases are observed in Europe. However, the circulation of toxigenic strains is still observed in all parts of the world, posing a constant threat to the population with low levels of seroprotection. More recently, Corynebacterium ulcerans has been increasingly isolated as emerging zoonotic agent of diphtheria from companion animals such as cats or dogs, indicating the enduring threat of this thought-to-be controlled disease.

• Application of resequencing microarrays in microbial detection and characterization.

  Authors: Tomasz A Leski, Baochuan Lin, Anthony P Malanoski, David A Stenger

  Future microbiology. 7:625-37.

  Microarrays are powerful, highly parallel assays that are transforming microbiological diagnostics and research. The adaptation of microarray-based resequencing technology for microbial detection andMicroarrays are powerful, highly parallel assays that are transforming microbiological diagnostics and research. The adaptation of microarray-based resequencing technology for microbial detection and characterization resulted in the development of a number assays that have unique advantages over other existing technologies. This technological platform seems to be especially useful for sensitive and high-resolution multiplexed diagnostics for clinical syndromes with similar symptoms, screening environmental samples for biothreat agents, as well as genotyping and whole-genome analysis of single pathogens.

• Development of humanized mouse models to study human malaria parasite infection.

  Authors: Ashley M Vaughan, Stefan Hi Kappe, Alexander Ploss, Sebastian A Mikolajczak

  Future microbiology. 7:657-65.

  Malaria is a disease caused by infection with Plasmodium parasites that are transmitted by mosquito bite. Five different species of Plasmodium infect humans with severe disease, but human malaria isMalaria is a disease caused by infection with Plasmodium parasites that are transmitted by mosquito bite. Five different species of Plasmodium infect humans with severe disease, but human malaria is primarily caused by Plasmodium falciparum. The burden of malaria on the developing world is enormous, and a fully protective vaccine is still elusive. One of the biggest challenges in the quest for the development of new antimalarial drugs and vaccines is the lack of accessible animal models to study P. falciparum infection because the parasite is restricted to the great apes and human hosts. Here, we review the current state of research in this field and provide an outlook of the development of humanized small animal models to study P. falciparum infection that will accelerate fundamental research into human parasite biology and could accelerate drug and vaccine design in the future.

• Mass gatherings and the implications for the spread of infectious diseases.

  Authors: Jen Kok, Christopher C Blyth, Dominic E Dwyer

  Future microbiology. 7:551-3.

• The postantifungal and paradoxical effects of echinocandins against Candida spp.

  Authors: Brad Moriyama, Stacey A Henning, Scott R Penzak, Thomas J Walsh

  Future microbiology. 7:565-9.

  Evaluation of: Shields RK, Nguyen MH, Press EG, Clancy CJ. Five-minute exposure to caspofungin results in prolonged postantifungal effects and eliminates the paradoxical growth of Candida albicans.Evaluation of: Shields RK, Nguyen MH, Press EG, Clancy CJ. Five-minute exposure to caspofungin results in prolonged postantifungal effects and eliminates the paradoxical growth of Candida albicans. Antimicrob. Agents Chemother. 55(7), 3598-3602 (2011). Echinocandins induce a postantifungal effect and a paradoxical effect. The postantifungal effect is a concentration-dependent process that allows for sustained kill of Candida spp. after relatively brief exposures to a compound. The paradoxical effect is growth that occurs at high echinocandin concentrations above the MIC. Paradoxical growth varies in terms of media, species, strain and type of echinocandin. The study by Shields et al. evaluated the impact of a brief exposure of caspofungin on paradoxical growth and postantifungal effects in Candida albicans isolates. In the postantifungal effect experiments, prolonged concentration-dependent killing occurred. Maximum postantifungal effects occurred with caspofungin exposures of 5 or 15 min. A brief exposure of caspofungin eliminated the paradoxical growth that was observed in the time-kill experiments. The report by Shields et al. illustrates that short exposures to an echinocandin may lead to prolonged postantifungal effects and furthers our understanding of the paradoxical effect in C. albicans.

• Human CMV transcripts: an overview.

  Authors: Yanping Ma, Ning Wang, Mali Li, Shuang Gao, Lin Wang, Bo Zheng, Ying Qi, Qiang Ruan

  Future microbiology. 7:577-93.

  The human CMV (HCMV) genome consists of an approximately 230-kb dsDNA and is predicted to contain over 165 open reading frames. Although the entire sequence of the laboratory-adapted AD169 strain ofThe human CMV (HCMV) genome consists of an approximately 230-kb dsDNA and is predicted to contain over 165 open reading frames. Although the entire sequence of the laboratory-adapted AD169 strain of HCMV was first available in 1991, the precise number and nature of viral genes and gene products are still unclear. Fewer than 100 predicted genes have been convincingly elucidated with respect to their expression patterns, transcript structure and transcription characteristics. The high gene number of HCMV creates a crowded genome with many overlapping transcriptional units. 3´- or 5´-coterminal overlapping polycistronic transcripts could use a common promoter element or a poly-A signal. 3´-coterminal monocistronic transcripts could encode 'nested' open reading frames, which possess different initiation but the same termination sites. As a virus with eukaryotic cells as the host, HCMV has the capacity to splice out introns during transcription. Major alternately spliced mRNA species of HCMV originate primarily, but not exclusively, from the immediate early gene regions. Alternate splicing patterns of the mRNAs could encode a number of gene products with different sizes. In recent years, some antisense and noncoding transcripts of HCMV have been reported. These RNAs probably have functions in genomic replication or the regulation of gene expression.

• Interactions between Streptococcus pneumoniae and influenza virus: a mutually beneficial relationship?

  Authors: Kirsty R Short, Marrit N Habets, Peter Wm Hermans, Dimitri A Diavatopoulos

  Future microbiology. 7:609-24.

  Historically, most research on infectious diseases has focused on infections with single pathogens. However, infections with pathogens often occur in the context of pre-existing viral and bacterialHistorically, most research on infectious diseases has focused on infections with single pathogens. However, infections with pathogens often occur in the context of pre-existing viral and bacterial infections. Clinically, this is of particular relevance for coinfections with Streptococcus pneumoniae and influenza virus, which together are an important cause of global morbidity and mortality. In recent years new evidence has emerged regarding the underlying mechanisms of influenza virus-induced susceptibility to secondary pneumococcal infections, in particular regarding the sustained suppression of innate recognition of S. pneumoniae. Conversely, it is also increasingly being recognized that there is not a unidirectional effect of the virus on S. pneumoniae, but that asymptomatic pneumococcal carriage may also affect subsequent influenza virus infection and the clinical outcome. Here, we will review both aspects of pneumococcal influenza virus infection, with a particular focus on the age-related differences in pneumococcal colonization rates and invasive pneumococcal disease.

• Invasive fungal infections in solid organ transplant recipients.

  Authors: Shmuel Shoham, Kieren A Marr

  Future microbiology. 7:639-55.

  Invasive fungal infections are a major problem in solid organ transplant (SOT) recipients. Overall, the most common fungal infection in SOT is candidiasis, followed by aspergillosis andInvasive fungal infections are a major problem in solid organ transplant (SOT) recipients. Overall, the most common fungal infection in SOT is candidiasis, followed by aspergillosis and cryptococcosis, except in lung transplant recipients, where aspergillosis is most common. Development of invasive disease hinges on the interplay between host factors (e.g., integrity of anatomical barriers, innate and acquired immunity) and fungal factors (e.g., exposure, virulence and resistance to prophylaxis). In this article, we describe the epidemiology and clinical features of the most common fungal infections in organ transplantation. Within this context, we review recent advances in diagnostic modalities and antifungal chemotherapy, and their impact on evolving prophylaxis and treatment paradigms.

• Thinking outside the box: new strategies for antichlamydial control.

  Authors: Raphael H Valdivia

  Future microbiology. 7:427-9.

• Endothelial cells and CMV dissemination.

  Authors: Giuseppe Gerna

  Future microbiology. 7:441-4.

  Evaluation of: Sacher T, Andrassy J, Kalnins A et al. Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination. PLoS Pathog. 7(11), E1002366 (2011). Using the murineEvaluation of: Sacher T, Andrassy J, Kalnins A et al. Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination. PLoS Pathog. 7(11), E1002366 (2011). Using the murine CMV animal model and the well-established model of Cre-lox-P-mediated green-fluorescence tagging of endothelial cell (EC)-derived mouse CMV to quantify the role of infected ECs in transplantation-associated CMV dissemination (in mice expressing Cre recombinase under the control of either the Tie2 or the Tek promoter selectively expressed in vascular EC-Tie-Cre and Tek-Cre mice), it was shown that EC-derived virus contributed to 50% of the total viral load during primary infection, and there was no preference for dissemination of EC-derived viruses over viruses produced by other cell types. In addition, during secondary viremia, there was only a negligible contribution of EC-derived virus to dissemination to other organs. These results are novel in the methodology employed and are somewhat interesting. However, the data are limited to the mouse model with a short-term follow-up, and the immunodeficient host has not yet been studied. In humans, these conclusions must be taken with caution. First, in primary infection occurring through natural routes, epithelial cells are infected first, then ECs, unless primary infection occurs through blood transfusion, in which case endothelial vascular cells may become infected first. In both cases, the virus transport occurs through the intervention of leukocytes, namely monocytes and polymorphonuclear leukocytes. As monocytes differentiate to macrophages, they become highly susceptible to human CMV replication inside organ tissues, while polymorphonuclear leukocytes are active in virus capturing from infected endothelial vascular cells and transporting to distant sites.

• Probing the cellular effects of bacterial effector proteins with the Yersinia toolbox.

  Authors: Stefan Wölke, Jürgen Heesemann

  Future microbiology. 7:449-56.

  The type 3 secretion system (T3SS) is a powerful bacterial nanomachine that is able to modify the host cellular immune defense in favor of the pathogen by injection of effector proteins. In thisThe type 3 secretion system (T3SS) is a powerful bacterial nanomachine that is able to modify the host cellular immune defense in favor of the pathogen by injection of effector proteins. In this regard, cellular Rho GTPases such as Rac1, RhoA or Cdc42 are targeted by a large group of T3SS effectors by mimicking cellular guanine exchange factors or GTPase-activating proteins. However, functional analysis of one type of T3SS effector that is translocated by bacterial pathogens is challenging because the T3SS effector repertoire can comprise a large number of proteins with redundant or interfering functions. Therefore, we developed the Yersinia toolbox to either analyze singular effector proteins of Yersinia spp. or different bacterial species in the context of bacterial T3SS injection into cells. Here, we focus on the WxxxE guanine exchange factor mimetic proteins IpgB1, IpgB2 and Map, which activate Rac1, RhoA or Cdc42, respectively, as well as the Rho GTPase inactivators YopE (a GTPase-activating mimetic protein) and YopT (cysteine protease), to generate a toolbox module for Rho GTPase manipulation.

• Viral and host factors that contribute to pathogenicity of enterovirus 71.

  Authors: Hsing-I Huang, Kuo-Feng Weng, Shin-Ru Shih

  Future microbiology. 7:467-79.

  The single-stranded RNA virus enterovirus 71 (EV71), which belongs to the Picornaviridae family, has caused epidemics worldwide, particularly in the Asia-Pacific region. Most EV71 infections resultThe single-stranded RNA virus enterovirus 71 (EV71), which belongs to the Picornaviridae family, has caused epidemics worldwide, particularly in the Asia-Pacific region. Most EV71 infections result in mild clinical symptoms, including herpangina and hand, foot and mouth disease. However, serious pathological complications have also been reported, especially for young children. The mechanisms of EV71 disease progression remain unclear. The pathogenesis of adverse clinical outcomes may relate to many factors, including cell tropism, cell death and host immune responses. This article reviews the recent advances in the identification of factors determining EV71 cell tropism, the associated mechanisms of viral infection-induced cell death and the interplay between EV71 and immunity.

• Oxidative stress resistance in Porphyromonas gingivalis.

  Authors: Leroy G Henry, Rachelle Me McKenzie, Antonette Robles, Hansel M Fletcher

  Future microbiology. 7:497-512.

  Porphyromonas gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiologic agent of periodontal disease. The harsh inflammatory condition of the periodontal pocket implies thatPorphyromonas gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiologic agent of periodontal disease. The harsh inflammatory condition of the periodontal pocket implies that this organism has properties that will facilitate its ability to respond and adapt to oxidative stress. Because the stress response in the pathogen is a major determinant of its virulence, a comprehensive understanding of its oxidative stress resistance strategy is vital. We discuss multiple mechanisms and systems that clearly work in synergy to defend and protect P. gingivalis against oxidative damage caused by reactive oxygen species. The involvement of multiple hypothetical proteins and/or proteins of unknown function in this process may imply other unique mechanisms and potential therapeutic targets.

• Intravital models of infection lay the foundation for tissue microbiology.

  Authors: Ferdinand X Choong, Jakob Regberg, Klas I Udekwu, Agneta Richter-Dahlfors

  Future microbiology. 7:519-33.

  In complex environments, such as those found in the human host, pathogenic bacteria constantly battle the unfavorable conditions imposed by the host response to their presence. During EscherichiaIn complex environments, such as those found in the human host, pathogenic bacteria constantly battle the unfavorable conditions imposed by the host response to their presence. During Escherichia coli-induced pyelonephritis, a cascade of events are shown in an intravital animal model to occur in a timely and sequential manner, representing the dynamic interplay between host and pathogen. Today, intravital techniques allow for observing infection in the living host. At resolutions almost on the single-cell level, improved detection methods offer a movie-like description of infection dynamics. Tissue microbiology involves monitoring host-pathogen interaction within the dynamic microecology of infectious sites in the live host. This new field holds great promise for insightful research into microbial disease intervention strategies.

• Back to the future: host-targeted chemotherapeutics for drug-resistant TB.

  Authors: Ruth J Napier, Thomas M Shinnick, Daniel Kalman

  Future microbiology. 7:431-5.

• Flexicate molecules as a potential new class of antibiotics.

  Authors: Devon L Rasmussen, Scott D Kobayashi, Frank R Deleo

  Future microbiology. 7:445-8.

  Evaluation of: Howson SE, Bolhuis A, Brabec V et al. Optically pure, water-stable metallo-helical 'flexicate' assemblies with antibiotic activity. Nat. Chem. 4(1), 31-36 (2011). Helicates areEvaluation of: Howson SE, Bolhuis A, Brabec V et al. Optically pure, water-stable metallo-helical 'flexicate' assemblies with antibiotic activity. Nat. Chem. 4(1), 31-36 (2011). Helicates are α-helical, nonpeptide complexes that bind to DNA and exhibit antimicrobial activity. In the past, enthusiasm for the use of helicates in biological applications was limited, at least in part, by the presence of a racemic mixture of enantiomers or the formation of complexes that are insoluble in aqueous solutions. Recently, Howson et al. overcame the barriers associated with helicate synthesis by generating helicate-like complexes that are soluble and stable in water, optically pure and synthetically flexible. The mechanism synthesizes nonpeptide mimetic α-helical 'flexicates' that bind to DNA and show broad-spectrum antimicrobial activity against representative Gram-positive and Gram-negative bacterial pathogens. Although the application of flexicates as an antimicrobial therapy remains to be determined, this study provides important insight into flexicate activity and the prospective use of flexicates as microbicidal agents.

• Prevention of acute otitis media using currently available vaccines.

  Authors: Nicola Principi, Elena Baggi, Susanna Esposito

  Future microbiology. 7:457-65.

  Acute otitis media (AOM) is common in infants and children. Although approximately two-thirds of cases are due to bacteria, almost all of the episodes are preceded by upper respiratory viralAcute otitis media (AOM) is common in infants and children. Although approximately two-thirds of cases are due to bacteria, almost all of the episodes are preceded by upper respiratory viral infection. Several viruses, among which respiratory syncytial virus is the most common, are involved in the determination of AOM. However, a significant number of AOM cases are associated with influenza infection, and influenza viruses are among the most frequently found respiratory viruses in the middle ear fluid during an acute episode of AOM. Consequently, influenza vaccination may have a favorable impact on the incidence and course of AOM. Moreover, as Streptococcus pneumoniae is one of the leading AOM bacterial pathogens and it is well known that influenza virus infection predisposes to pneumococcal infection, there is a further reason to suggest the use of influenza vaccine to reduce the risk of AOM. On the other hand, the administration of pneumococcal conjugate vaccine is considered per se a possible means of reducing the incidence of the disease. However, although a number of studies have measured the impact of both vaccines on AOM, it is still not known whether (and to what extent) they are really effective, nor what impact the more recently licensed vaccines may have. The aim of this review is to examine the clinical impact of vaccinations on AOM.

• Human challenge studies: a review of adequacy of reporting methods and results.

  Authors: Jennifer A Kalil, Scott A Halperin, Joanne M Langley

  Future microbiology. 7:481-95.

  Since the 1940s, researchers have purposefully infected healthy adult humans with pathogenic organisms to study how these pathogens cause disease and can be treated and prevented. 'Challenge studies'Since the 1940s, researchers have purposefully infected healthy adult humans with pathogenic organisms to study how these pathogens cause disease and can be treated and prevented. 'Challenge studies' can be safe, ethical, extremely informative and an efficient use of resources during the clinical development of vaccines, but knowledge of this form of clinical research trial is not widespread. A review of the human challenge literature was performed to determine whether common elements of challenge studies can be identified in the articles published to date. The review demonstrated incomplete reporting of study characteristics deemed necessary for the correct interpretation and application of human challenge study results and for the accurate replication of study methodology. An unofficial extension of the Consolidated Standards of Reporting Trials (CONSORT) statement is proposed.

• How Mycobacterium tuberculosis goes to sleep: the dormancy survival regulator DosR a decade later.

  Authors: Calvin Boon, Thomas Dick

  Future microbiology. 7:513-8.

  With 2 million deaths per year, TB remains the most significant bacterial killer. The long duration of chemotherapy and the large pool of latently infected people represent challenges in diseaseWith 2 million deaths per year, TB remains the most significant bacterial killer. The long duration of chemotherapy and the large pool of latently infected people represent challenges in disease control. To develop drugs that effectively eradicate latent infection and shorten treatment duration, the pathophysiology of the causative agent Mycobacterium tuberculosis needs to be understood. The discovery that the tubercle bacillus can develop a drug-tolerant dormant form and the identification of the underlying genetic program 10 years ago paved the way for a deeper understanding of the life of the parasite inside human lesions and for new approaches to antimycobacterial drug discovery. Here, we summarize what we have learnt since the discovery of the master regulator of dormancy, DosR, and the key gaps in our knowledge that remain. Furthermore, we discuss a possible wider clinical relevance of DosR for 'nontuberculous mycobacteria'.

• Identification by cDNA cloning of abundant sRNAs in a human-avirulent Yersinia pestis strain grown under five different growth conditions.

  Authors: Yi Qu, Lijun Bi, Xiaolan Ji, Zhongliang Deng, Hongtai Zhang, Yanfeng Yan, Ming Wang, Aqian Li, Xinxiang Huang, Ruifu Yang, Yanping Han

  Future microbiology. 7:535-47.

  Aims: sRNA regulation is supposedly involved in the stress response of a pathogen during infection. Yersinia pestis, the etiologic agent of plague, must encounter temperature and microenvironmentAims: sRNA regulation is supposedly involved in the stress response of a pathogen during infection. Yersinia pestis, the etiologic agent of plague, must encounter temperature and microenvironment changes, given its lifestyle. Here, we used the cDNA cloning approach to discover full-length sRNA candidates that are highly expressed in Y. pestis under five different growth conditions. Materials & methods: The cDNA cloning approach was improved by combining the traditional cDNA library construction with the prevalent rapid amplification of cDNA ends and RNA size selection techniques. Results: In total, 43 RNA species, including six previously annotated sRNAs, were identified. Of these, 25 sRNAs were encoded on the antisense strand of the annotated genes. Interestingly, two of these sRNAs were found on the complementary strand of noncoding RNAs. In addition, eight novel sRNAs encoded in the intergenic regions were also revealed. Ten sRNA candidates chosen for the northern blot analysis were successfully detected. Analysis of the expression patterns of 29 candidate sRNAs showed that 24 sRNAs are highly abundant in Y. pestis upon entry into the stationary growth phase. Conclusion: Our preliminary attempt at screening the novel sRNA candidates will lay the foundation for understanding the roles of sRNAs in Y. pestis physiology and pathogenesis.

• Challenges in assessing associations between hormonal contraceptive use and the risks of HIV-1 acquisition and transmission.

  Authors: Maria J Wawer, Ronald H Gray

  Future microbiology. 7:315-8.

  Evaluation of: Heffron R, Donnell D, Rees H et al.; for the Partners in Prevention HISV/HIV Transmission Study Team. Use of hormonal contraceptives and risk of HIV-1 transmission: a prospectiveEvaluation of: Heffron R, Donnell D, Rees H et al.; for the Partners in Prevention HISV/HIV Transmission Study Team. Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study. Lancet Infect. Dis. 12(1), 19-26 (2012). Prior observational studies produced inconsistent findings regarding hormonal contraception (HC) and risks of HIV acquisition and transmission. Heffron et al. conducted secondary data analyses on 3790 HIV discordant couples enrolled in two studies (a randomized trial of HSV-2 suppression and a study of immune correlates of HIV-1 protection) to assess HIV-1 acquisition and transmission in relation to HC use in females. HIV incidence among female HC nonusers was 3.8/100 person years (py), compared to 6.9/100 py among injectable users (p = 0.04) and 5.9/100 py in oral contraceptive users (p = 0.33). Among men, HIV incidence was 1.5/100 py in partners of HIV-positive HC nonusers, compared to 2.6/100 py in partners of injectable users (p < 0.05) and 2.5/100 py in men whose HIV-infected partners used oral contraceptives (p = 0.31). Study strengths included frequent follow up, excellent retention, known HIV exposure and viral load in the index infected partner, genetic linkage of virus from both partners and sexual behavior information. However, confounding by factors that cannot be controlled, including misreporting of condom use, is likely, given participants' high pregnancy rates. Clinicians and clients need to balance potential HC risks with the known risks of unwanted pregnancies. Condom use remains essential for HIV prevention regardless of other contraceptive usage.

• Hepatitis A virus evolution and the potential emergence of new variants escaping the presently available vaccines.

  Authors: Rosa M Pintó, Lucía D'Andrea, Francisco J Pérez-Rodriguez, M Isabel Costafreda, Enric Ribes, Susana Guix, Albert Bosch

  Future microbiology. 7:331-46.

  Hepatitis A is the most common infection of the liver worldwide and is fecal-orally transmitted. Its incidence tends to decrease with improvements in hygiene conditions but at the same time itsHepatitis A is the most common infection of the liver worldwide and is fecal-orally transmitted. Its incidence tends to decrease with improvements in hygiene conditions but at the same time its severity increases. Hepatitis A virus is the causative agent of acute hepatitis in humans and belongs to the Hepatovirus genus in the Picornaviridae family, and it has very unique characteristics. This article reviews some molecular and biological properties that allow the virus to live in a very quiescent way and to build an extremely stable capsid that is able to persist in and out of the body. Additionally, the relationship between the genomic composition and the structural and antigenic properties of the capsid is discussed, and the potential emergence of antigenic variants is evaluated from an evolutionary perspective.

• Post-translational modifications of host proteins by Legionella pneumophila: a sophisticated survival strategy.

  Authors: Monica Rolando, Carmen Buchrieser

  Future microbiology. 7:369-81.

  Eukaryotic proteins are tightly regulated by post-translational modifications, leading to a very subtle degree of regulation in time and space. Pathogen-mediated post-translational modifications areEukaryotic proteins are tightly regulated by post-translational modifications, leading to a very subtle degree of regulation in time and space. Pathogen-mediated post-translational modifications are key strategies to modulate host factors by targeting central signaling pathways in the host cell. Legionella pneumophila, an intracellular pathogen that coevolved with protozoan hosts, encodes a large arsenal of secreted effectors conferring the ability to evade host cellular defenses and to manipulate them to promote invasion and intracellular replication. Conservation of many signaling pathways of protozoa in human macrophages confers the ability of L. pneumophila to infect humans, causing a severe pneumonia called legionnaires' disease. Most of the secreted proteins are delivered by the Dot/Icm type IV secretion system and several of these have been shown to act on different cellular pathways critical for infection. Moreover, multiple effectors target a single host function to orchestrate bacterial survival. In this review, we focus on those effectors in the repertoire of L. pneumophila proteins that target key cellular pathways by specific post-translational modifications.

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