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George F Sensabaugh

Publications and source records attributed to George F Sensabaugh.

7 recordsLinked to original sources

The ompA gene in Chlamydia trachomatis differs in phylogeny and rate of evolution from other regions of the genome.

Strains of Chlamydia trachomatis are classified into serovars based on nucleotide sequence differences in ompA, the gene that encodes the major outer membrane protein. Phylogenetic characterization of strains based on ompA, however, results in serovar groupings that are inconsistent with the distinguishing features of C. trachomatis pathobiology, e.g., tissue tropisms and disease presentation. We have compared nucleotide sequences at multiple sites distributed around the chlamydial genome from 18 strains representing 16 serovars; sampled regions included genes encoding housekeeping enzymes (totaling 2,073 bp), intergenic noncoding segments (1,612 bp), and a gene encoding a second outer membrane protein (porB; 1,023 bp), with the ompA sequence (1,194 bp) used for reference. These comparative analyses revealed substantial variation in nucleotide substitution patterns among the sampled regions, with average pairwise sequence differences ranging from 0.15% for the housekeeping genes to 12.1% for ompA. Phylogenetic characterization of the sampled genomic sequences yielded a strongly supported tree that divides the strains into groupings consistent with C. trachomatis biology and which has a topology quite distinct from the ompA tree. This phylogenetic incongruity can be accounted for by recombination of the ompA gene between different genomic backgrounds. We found, however, no evidence of recombination within or between any of the sampled regions around the C. trachomatis genome apart from ompA. Parallel analysis of published sequence data on four members of the pmp gene family are consistent with the phylogenetic analyses reported here.

Animals↗

Population dynamics of nasal strains of methicillin-resistant Staphylococcus aureus--and their relation to community-associated disease activity.

BACKGROUND: Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) plays a key role in the epidemiology and pathogenesis of disease. The purpose of this study was to determine the characteristics and dynamics of nasal strains of MRSA, as well as their relation to community-associated disease activity. METHODS: This study is a cross-sectional survey and molecular epidemiologic analysis of nasal colonization by S. aureus in homeless and runaway youths, an underserved population at high risk for staphylococcal disease. RESULTS: Of the 308 study participants, 27.6% carried S. aureus, and 6.2% carried MRSA. Subgroups of individuals with increased MRSA carriage rates were also at highest risk for community-associated MRSA infection; these subgroups included individuals with either HIV infection or AIDS, injection drug users, patients with abscesses, and those recently hospitalized. Multilocus sequence typing and pulsed-field gel electrophoresis identified 2 genotypes--ST59:P (USA1000) and ST8:S (USA300)--that accounted for 84.2% (16/19) of the MRSA isolates carried. The genotypes were distinct from nosocomial genotypes endemic in the hospital, although they originated from individuals with prior exposure to health care. CONCLUSIONS: Comparison of MRSA strains from asymptomatic carriers versus concurrently collected community-associated clinical strains from patients treated at local health-care facilities allowed for the identification of 3 population dynamics of nasal strains of MRSA: (1) endemic clones--for example, ST8:C and ST59:P--sustained asymptomatic carriage and infection over prolonged periods; (2) an epidemic clone, ST8:S, demonstrated enhanced capacity for rapid transmission and widespread infections; and (3) an outbreak clone, ST30:Z (USA1100), was highly infectious but exhibited poor asymptomatic transmission.

Adolescent↗

Community-adapted methicillin-resistant Staphylococcus aureus (MRSA): population dynamics of an expanding community reservoir of MRSA.

To define methicillin-resistant Staphylococcus aureus (MRSA) reservoirs in the community and their population dynamics, we studied the molecular epidemiology of a random sample (n=490) from a collection of 2154 inpatient and outpatient MRSA isolates during a 7-year period in San Francisco. We noted a progressive replacement of type II staphylococcal chromosomal cassette (SCC)mec-bearing isolates with type IV SCCmec-bearing isolates, which coincided with >4-fold increase in methicillin resistance between 1998 and 2002. Type IV SCCmec-bearing isolates involved in the increase in methicillin resistance belonged to 4 molecular genotypes. These 4 genotypes were associated predominantly with community-onset disease, rather than hospital- or long-term-care facility-onset disease (76.9% vs. 19.4% vs. 3.7%; P=.0005), suggesting that they are not feral descendants of hospital isolates. The longitudinal results linked the dramatic increase in MRSA infections to an expanding community reservoir of MRSA genotypes with intrinsic community survival advantage.

Anti-Bacterial Agents↗

Widespread skin and soft-tissue infections due to two methicillin-resistant Staphylococcus aureus strains harboring the genes for Panton-Valentine leucocidin.

Infections caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are emerging as a major public health problem. CA-MRSA has been associated previously with skin and soft-tissue infection (SSTI) and with carriage of staphylococcal cassette chromosome mec (SCCmec) type IV and the Panton-Valentine leucocidin (PVL) virulence factor. To assess the clonal distribution of PVL-carrying strains and the association with SSTI in the San Francisco Bay area, we surveyed six collections of S. aureus isolates-671 isolates in all-collected between 1997 and 2002 originating from inpatient and outpatient clinical specimens and from a community-based sampling. Isolates were genotyped by pulsed-field gel electrophoresis, multilocus restriction fragment typing, and multilocus sequence typing and assayed for the PVL virulence factor. The S. aureus populations showed a high proportion of PVL-carrying strains, with frequencies ranging up to 70% in MRSA isolated from jail inmate patients and 69% in MRSA from patients receiving surgical treatment at an outpatient clinic specializing in treating SSTIs. PVL-carrying isolates were identified in nine clonal groups, but 88.5% of the PVL-carrying MRSA isolates belonged to only two clonal groups. These two clonal groups carried the SCCmec type IV resistance determinant and were more likely than other clonal groups to be recovered from SSTI sites than from other sites (P < 0.0001). There is evidence of clonal replacement over the period from 1999 to 2002, with one of these two clonal groups being supplanted by the other.

Bacterial Toxins↗

Increasing prevalence of methicillin-resistant Staphylococcus aureus infection in California jails.

Staphylococcus aureus clinical isolates obtained from patients who were inmates of the San Francisco County jail system showed an increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) from 29%, in 1997, to 74%, in 2002; 91% of the MRSA isolates carried staphylococcal chromosomal cassette mec (SCCmec) type IV. Pulsed field gel electrophoresis and multilocus sequence typing demonstrated 2 major clonal groups. One of these clonal groups is genetically indistinguishable from the strain responsible for an outbreak of MRSA in the Los Angeles County jail system in 2002.

Anti-Bacterial Agents↗

Clonal characterization of Staphylococcus aureus by multilocus restriction fragment typing, a rapid screening approach for molecular epidemiology.

We have developed a rapid and simplified approach for the strain characterization of Staphylococcus aureus on the basis of multilocus sequence typing (MLST) in which sequence variations in the MLST housekeeping gene loci are detected by restriction fragment pattern analysis rather than sequencing; we refer to this approach as multilocus restriction fragment typing (MLRFT). Briefly, MLRFT for S. aureus involves the PCR amplification of each of the seven MLST housekeeping gene loci by using the same primer pairs used in MLST. The amplicons are then digested directly with one or two restriction enzymes and the restriction fragments are resolved by agarose gel electrophoresis. Projection from published MLST data shows that MLRFT captures about 95% of the genetic diversity detected by MLST. The MLRFT approach was validated with a set of 59 methicillin-susceptible and 44 methicillin-resistant S. aureus isolates from community-acquired and nosocomial sources which had previously been characterized by pulsed-field gel electrophoresis (PFGE). MLRFT resolved the 103 isolates into 15 restriction fragment types, giving a discrimination index of 89.0%. Clonal groupings established by MLRFT correlated well with those established by PFGE. In short, MLRFT provides a convenient alternative to MLST and PFGE because it requires minimal laboratory facilities and is relatively simple and inexpensive to perform.

Alleles↗