Tips from the Journals of the American Society for Microbiology

New Antibiotic Shows Promise in Fighting Malaria

A new study suggests that tigecycline, the first member of a new class of antibiotics, shows significant antimalarial activity on its own and may also be effective against multi drug-resistant malaria when administered in combination with traditional antimalarial drugs. The researchers from the Medical University of Vienna, Austria; Malaria Research Initiative Bandarban, Bangladesh; and the International Center for Diarrheal Disease Research, Dhaka, Bangladesh report their findings in the September 2009 issue of the journal Antimicrobial Agents and Chemotherapy.

Increasing resistance of Plasmodium falciparum to existing drugs has resulted in the search for new antimalarial therapies. Tigecycline belongs to a novel class of antibiotics called glycylcyclines which exhibit unique and novel methods of action against bacteria and are specifically designed to overcome two mechanisms of tetracycline resistance. Clinical studies of tigecycline have shown it is easy to administer and is generally well tolerated with a twice-daily dosing regimen.

In the study blood samples were collected from male and nonpregnant female patients in Bangladesh infected by P. falciparum. Specifically excluded from the study were pregnant or breastfeeding women and patients who had received malaria drug therapy up to 30 days prior. When tested with 66 isolates tigecycline showed one the highest activities of all antibiotics against P. falciparum. Additionally, tigecycline was up to 6 times more active against P. falciparum than doxycycline, however, when tested in conjunction with doxycycline, a significant activity correlation was noted. Finally, further testing of tigecycline confirmed earlier studies indicating that tigecycline may induce a delayed-death response and also that it has a relatively long half-life making it simpler to administer than tetracycline and doxycycline.

“We conclude that tigecycline has substantial antimalarial activity on its own and may be a potential candidate for exploring its clinical efficacy in combination with faster-acting antimalarials in the parenteral treatment of multidrug-resistant P. falciparum malaria in seriously ill patients,” say the researchers.

(P. Starzengruber, K. Thriemer, R. Haque, W.A. Khan, H.P. Fuehrer, A. Siedl, V. Hofecker, B. Ley, W.H. Wernsdorfer, H. Noedl. 2009. Antimalarial activity of tigecycline, a novel glycylcycline antibiotic. Antimicrobial Agents and Chemotherapy, 53. 9: 4040-4042.)

Can Gene Expression Profiling make it Possible to Predict Deadly Infections in Cattle?

A new study suggests that gene expression profiling may allow researchers to track the progression of bovine spongiform encephalopathy (BSE) in cattle and ultimately predict their infectious status. The researchers from the Veterinary Laboratories Agency, Woodham Lane, New Haw, Surrey, United Kingdom and Ludwig-Maximilians-University Munich, Germany detail their findings in the September 2009 issue of the Journal of Virology.

Prion diseases are transmissible, and inevitably fatal, neurodegenerative disorders that are responsible for BSE in cattle, Creutzfeldt-Jakob disease (CJD) in humans, and scrapie in sheep and goats. The first cases of BSE were reported in the United Kingdom in 1986 and reached epidemic proportions by 1992 at which point up to 185,000 cattle had succumbed to the disease. Contaminated meat and bone meal, common dietary supplements, are believed to be the cause of oral infection in cattle and BSE is considered to be the origin of the human disease variant of which there have been approximately 200 cases worldwide. Current research suggests that an abnormality of the cellular prion protein is essential to the infectivity of prion disease, indicating a correlation between BSE pathogenesis and gene expression.

In the study brain tissue samples were collected from cattle orally infected with BSE at varying time points following postinfection and monitored for changes in gene expression. Researchers found that 114 genes were differentially regulated over the course of infection, many of which encode proteins involved in functions such as immune response, stress response and cell adhesion. The largest number of differentially regulated genes was detected at 21 months postinfection indicating many pathogenic processes in the animal brain prior to detection of BSE in the central nervous system.

“Gene expression profiling in the BSE time course study revealed a broad correlation between the expression of genes and the progression of BSE,” say the researchers. “Evidence is presented to suggest that it is possible to predict the infectious status of animals using the expression profiles from this study.”

(Y. Tang, W. Xiang, S.A.C. Hawkins, H.A. Kretzschmar, O. Windl. 2009. Transcriptional changes in the brains of cattle orally infected with the bovine spongiform encephalopathy agent precede detection of infectivity. Journal of Virology, 83. 18: 9464-9473.)

Common Viral Infection in Infants May Persist Long-term in the Central Nervous System

A new study suggests that coxsackievirus, a significant human pathogen that commonly infects the central nervous system of newborns, may persist in the body as a low-level, long-term infection causing ongoing inflammatory lesions. This discovery disputes previous beliefs that while acute, coxsackievirus is also self-limiting. The researchers report their findings in the September 2009 issue of the Journal of Virology.

Coxsackievirus is a commonly occurring childhood infection that afflicts the central nervous system. It is often diagnosed in newborns and can lead to complications such as meningitis, encephalitis, and death. Prior research indicates that infection of the central nervous system at an early age may result in severe physical and intellectual disabilities, deficiencies in scholastic performance, and even the development of neurological disorders such as schizophrenia later in life. A large percentage of polio victims are now experiencing new symptoms, known as postpolio syndrome, some fifty years after the primary infection suggesting we may be underestimating the lasting effects of childhood infections on the central nervous system.

In a previous study the researchers utilized a neonatal mouse model of coxsackievirus B3 (CVB3) to determine that stem cells in the central nervous system were preferentially targeted by the virus. The later stages of infection were the focus of this study in which the researchers examined the ensuing inflammatory response and lesions remaining in the adult central nervous systems of surviving mice from the previous model. Results showed high levels of interferons and chemokines up to 10 days postinfection as well as chronic inflammation and lesions in the brains of surviving mice up to 9 months postinfection. Additionally, CVB3 RNA was detected in the central nervous system at high abundance up to 3 months postinfection.

“These data suggest that CVB3 may persist in the CNS as a low-level, noncytolytic infection, causing ongoing inflammatory lesions,” say the researchers. “Thus, the effects of a relatively common infection during the neonatal period may be long lasting, and the prognosis for newborn infants recovering from acute infection should be reexplored.”

(R. Feuer, C.M. Ruller, N. An, J.M. Tobar-Godwin, R.E. Rhoades, S. Maciejewski, R.R. Pagarigan, C.T. Cornell, S.J. Crocker, W.B. Kiosses, N. Pham-Mitchell, I.L. Campbell, J.L. Whitton. 2009. Viral persistence and chronic immunopathology in the adult central nervous system following coxsackievirus infection during the neonatal period. Journal of Virology, 83. 18: 9356-9369.)

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