Segue
Population
Genetics
Population Genetics of Cryptosporidium
parvum
Research on the population genetics of Cryptosporidium parvum
is showing exciting developments. A study of numerous C. parvum
isolates of human and animal origin collected in a small area of Scotland
has uncovered differences in the epidemiology of what was originally referred
to as C. parvum type 1 (also, anthroponotic type) and type 2 (zoonotic
type), a designation recently changed to C. hominis and C. parvum.
This study, based on fingerprints obtained from eight polymorphic genetic
markers, showed striking differences between the population structure
of these species; a clonal C. hominis population and a more complex
C. parvum population. The population structure of C. hominis
was consistent with the epidemic nature of human infections, where a small
number of genotypes predominate. In contrast, C. parvum (type 2)
genetic fingerprints showed evidence of random mating among genetically
diverse parasites. Evidence for partitioning of the species according
to host (human and bovine) was also inferred from these data. Two questions
we are left with are whether these observations are specific to this particular
location, where human transmission is relatively infrequent, and whether
regions with high prevalence of human cryptosporidiosis will show more
complex structures in both species. If substructuring into human– and
bovine– derived C. parvum (type 2) is consistently observed, the
potential for zoonotic transmission of C. parvum may also have
to be reexamined.
Widmer G. Population
genetics of Cryptosporidium parvum. Trends Parasitol 2004;20:3–6;discussion
6. Available at: http://dx.doi.org/10.1016/j.pt.2003.10.010
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Diagnostic
Virology
Role for Arrays in Clinical
Virology: Fact or Fiction?
Polymerase chain reaction (PCR) detection of genomic DNA or RNA has become
an indispensable tool for the diagnosis and surveillance of viral disease.
Perhaps the biggest drawback of PCR, though, is that only one or a few
viruses can be searched for in a single test. DNA chips or microarrays
have the potential to overcome this disadvantage and can provide a near-patient
test that identifies both known viruses and those causing newly emerging
diseases such as SARS. For this potential to be realized, however, the
PCR techniques capable of amplifying any adventitious sequence in a clinical
specimen and the microarraying hybridization and detection technologies
necessary for obtaining rapid and reproducible results need to converge.
The arrays that have already been developed for use in virology point
the way forward.
Clewley JP. A
role for arrays in clinical virology: fact or fiction? J Clin Virol
2004; 29:2–12. Review. Available at: http://dx.doi.org/10.1016/j.jcv.2003.08.002
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Molecular
Epidemiology
Multilocus Sequence Typing
and the Evolution of Methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus (MRSA) continue to
adapt to the selective pressure of antimicrobial agents and to exploit
new niches, as evidenced by the recent isolation of strains with high-level
vancomycin resistance and the emergence of MRSA as a community pathogen.
The combined use of the bacterial genotyping technique, multilocus sequence
typing (MLST), and characterization of the mobile methicillin-resistance
determinant, staphylococcal chromosomal cassette mec (SCCmec),
has provided new insights into MRSA strain nomenclature, evolution, and
epidemiology. The first MRSA emerged when SCCmec was acquired
by an epidemic methicillin-susceptible strain prevalent in Europe. Acquisition
of SCCmec by other successful strains has led to the emergence
of at least 11 major epidemic MRSA strains belonging to five distinct
lineages with a global geographic distribution. These five lineages have
evolved both hospital-acquired and community-acquired MRSA, but some of
the newly emerging community strains descend from other lineages.
Robinson DA, Enright
MC. Multilocus
sequence typing and the evolution of methicillin-resistant Staphylococcus
aureus. Clin Microbiol Infect 2004;10:92–7.
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Vaccines
Mimicking Live Flavivirus
Immunization with a Noninfectious RNA Vaccine
A new genetic vaccine against flaviviruses is presented that can stimulate
a comprehensive immune response similar to a live vaccine but with the
safety profile of an inactivated vaccine. The principle is based on the
use of noninfectious but replication-competent genomic RNA. This vaccine
mimics live viral infection, although there is no spread of virus in the
body. The complete replication complex is expressed, including all viral
nonstructural proteins known to be targets of the humoral and cellular
immune response. In addition, subviral particles consisting of the viral
surface proteins prM/M and E are produced and presented to the immune
system. The proof-of-principle is demonstrated with tick-borne encephalitis
virus (TBEV). Because of the close genetic relationship among members
of the genus Flavivirus, this principle presumably can also be
applied to other pathogens of worldwide medical importance, such as dengue
viruses, Japanese encephalitis virus, yellow fever virus, and West Nile
virus. The vaccine consists of in vitro synthesized genomic RNA, genetically
modified to abolish viral infectivity but to provide ample production
and release of subviral particles. Gene-gun mediated injection of this
experimental TBEV vaccine into adult mice is shown to yield a neutralizing
and protective immune response.
Koffler RM, Aberle
JH, Aberle SW, Allison SL, Heinz FX, Mandl CW. Mimicking
live flavivirus immunization with a non-infectious RNA vaccine.
Proc Natl Acad Sci U S A 2004;101:1951–6. Epub 2004 Feb 09. Available
at: www.pnas.org/cgi/content/abstract/101/1951
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Ecology
Bacterial Biofilms: Prokaryotic
Adventures in Multicellularity
Three-dimensional bacterial biofilm microstructures display multicellular
characteristics in common with higher organisms, such as cell death and
differentiation during development, which carry several medical and evolutionary
implications. Biofilm microstructures appear to enhance bacterial tolerance
to a number of stresses, including antimicrobial agents; determinants
of multicellularity, such as cell-cell signaling, are necessary for this
tolerance. Processes of microcolony development and differentiation are
therefore of particular interest as targets for novel strategies to control
biofilms.
Webb JS, Givskov
M, Kjelleberg S. Bacterial
biofilms: prokaryotic adventures in multicellularity. Curr Opin
Microbiol 2003;6:578–85. Review. Available at: http://dx.doi.org/10.1016/j.mib.2003.10.014
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Pathogenesis
CCR5 and CXCR4 Co-Receptors
in HIV Infection
This article examined the central role played by co-receptor expression
and usage in the transmission and pathogenic effects of HIV-1 infection
of humans. The review contains a discussion of the HIV-1 phenotypic variants
defined by their use of the CCR5 or CXCR4 co-receptors. How the different
cellular tropism patterns of these viral variants influence how and where
HIV-1 replicates in vivo is also discussed, with emphasis on the thymus
and gut-associated lymphoid tissues. The review also contains a consideration
of the possible outcomes of the use of co-receptor antagonists as drugs
to treat HIV-1 infection in vivo.
Moore JP, Kitchen
SG, Pugach P, Zack, JA. The
CCR5 and CXCR4 coreceptors—central to understanding the transmission
and pathogenesis of human immunodeficiency virus type 1 infection.
AIDS Res Hum Retroviruses 2004;20:111–26.
About Segue
Segue presents brief summaries of articles on pertinent emerging issues
published elsewhere and is edited by Joseph E. McDade.
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