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Biomedical subjects

J Kornblum

Publications and source records attributed to J Kornblum.

At least 19 recordsLinked to original sources
PubMed2006

A recurring outbreak of Shigella sonnei among traditionally observant Jewish children in New York City: the risks of daycare and household transmission.

Dispersed community outbreaks of Shigella sonnei have occurred cyclically among traditionally observant Jews in the United States. In February 2000, we investigated a S. sonnei outbreak in one Jewish community in New York City. To determine risk factors for introduction of infection into households, we conducted a cohort study of households to compare risk factors for illness among primary subjects within households and age-matched well siblings. Isolates were subtyped by pulsed-field gel electrophoresis (PFGE). We used a random effects model to assess extra-household vs. intra-household transmission in households with multiple ill household members. Daycare or pre-school attendance [matched odds ratio (mOR) 16.1, P<0.001] and age <60 months (mOR 6.3, P<0.001) were independently associated with index subject illness. Outbreak isolates were closely related by PFGE analysis to the strain previously observed in Jewish community outbreaks. The random effects model strongly indicated that multiple illnesses in a single household are due to secondary transmission. Disease containment efforts should focus on reducing Shigella transmission in childcare settings and within homes.

Case-Control Studies↗
PubMed2000

Prevalence of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in the community.

Recent reports indicate that community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing and may now involve persons without risk factors predisposing for acquisition. To estimate the extent of community MRSA in New York City, the prevalence of S. aureus and MRSA nasal colonization in a well-patient population of 500 children and guardians was determined. The prevalence of S. aureus nasal carriage was 35% for children and 28% for guardians. One person with predisposing risk factors was colonized with an MRSA, which was identified as the predominant clone found in New York City hospitals. A high degree of methicillin-susceptible S. aureus strain diversity was noted, with no apparent selection for specific clonal types. Thus, MRSA colonization is not ubiquitous in persons without predisposing risk outside of the health care environment. Bacterial competition and a lack of strong selection may limit the community spread of MRSA and can account for its sporadic distribution.

Adolescent↗
PubMed2000

Streptococcus pneumoniae serotype 4 outbreak in a home for the aged: report and review of recent outbreaks.

OBJECTIVE: To describe a pneumonia outbreak caused by Streptococcus pneumoniae among residents of a home for the aged and to review contemporary pneumococcal outbreaks. DESIGN: Epidemiological investigation. METHODS: S pneumoniae isolates were serotyped and analyzed by pulsed-field gel electrophoresis. Paired sera were tested for antibodies to pneumococcal surface adhesin A protein (PsaA, a 37-kDa cell-wall protein). Pneumococcal outbreaks reported in the last decade in English were reviewed. RESULTS: Pneumonia developed in 18 of 200 residents. In 11 (61%), a pneumococcal etiology was demonstrated. S pneumoniae, serotype 4, was isolated from the blood cultures of 3 patients; all isolates were indistinguishable by pulsed-field gel electrophoresis. Pneumococcal involvement was established in 2 by sputum culture and latex agglutination of parapneumonic fluid and in 6 others by a twofold rise in optical density of serum antibody reactive to PsaA. Pneumococcal immunization had not previously been received by any patient; mortality was 22%. No additional cases were noted following administration of pneumococcal vaccine and antibiotic prophylaxis with penicillin or erythromycin. Twenty-six outbreaks of invasive pneumococcal disease since 1990 were reviewed. Twelve occurred in the United States, and serotypes 23F, 14, and 4 accounted for 8 (67%) of 12 outbreaks. All confirmed serotypes in US outbreaks are included in the 23-valent vaccine. More than one half of pneumococcal outbreaks worldwide involved elderly persons in hospitals or long-term-care facilities. CONCLUSIONS: A pneumococcal pneumonia outbreak occurred among unvaccinated residents of a residential facility for the aged. Institutionalized elderly persons are at risk of outbreaks of pneumococcal disease and should be vaccinated.

Aged↗
PubMed2000

Resistance rather than virulence selects for the clonal spread of methicillin-resistant Staphylococcus aureus: implications for MRSA transmission.

The population structure of methicillin-resistant Staphylococcus aureus (MRSA) is predominantly clonal, which may be related to the fitness of the genetic background of the methicillin-susceptible S. aureus (MSSA) into which the mecA chromosomal resistant determinant has inserted. To test this idea, we assessed whether the genotypes of New York MRSA are present in MSSA populations by using a combination of protein A gene sequence typing (spa typing) and pulsed-field gel electrophoresis (PFGE). Although about 16% of colonizing MSSA isolated from community subjects were related to MRSA, only one of the five predominant New York MRSA clonal types was found among the MSSA isolates. Similarly, among nosocomial MSSA, only four MRSA homologues were observed, two of which may have arisen through deletion of the mec element. Thus, MRSA clonal types represent a limited spectrum of the diversity seen in community and hospital S. aureus populations. The data are best explained by antibiotic selection pressure, as opposed to increased transmissibility or virulence, being responsible for the clonal dissemination of the resistance phenotype in MRSA genetic backgrounds, an in turn, the limited spread of these strains outside of the hospital environment.

Amino Acid Sequence↗
PubMed1999

Multicenter laboratory validation of susceptibility testing of Mycobacterium tuberculosis against classical second-line and newer antimicrobial drugs by using the radiometric BACTEC 460 technique and the proportion method with solid media.

In a large multicenter study involving six major study sites in the United States, Canada, and Europe, the susceptibilities of 272 Mycobacterium tuberculosis strains to classical second-line antituberculosis (anti-TB) drugs (capreomycin, cycloserine, ethionamide, and kanamycin) and newer compounds (amikacin, clofazimine, ofloxacin, and rifabutin) were determined by the radiometric BACTEC 460 procedure and the conventional proportion method on Middlebrook 7H10 agar. Previously established critical concentrations for classical second-line anti-TB drugs were compared with several concentrations in liquid medium to establish equivalence. MICs of newer compounds determined in liquid medium were either the same or up to four times lower than those determined in agar medium. After establishing critical concentrations (breakpoints) in the extended testing of clinical isolates, we obtained an excellent overall correlation between the two systems, with no errors with amikacin, kanamycin, and ofloxacin and very few major or very major errors with the other drugs; however, for cycloserine, no breakpoint concentration could be recommended due to repeatedly inconsistent results by both methods. Based on these data we conclude that the BACTEC 460 procedure is a simple and rapid method requiring 4 to 8 days on average to generate accurate antimicrobial susceptibility testing (AST) results for eight anti-TB drugs other than those considered primary ones. These data not only fill a major gap of knowledge regarding the critical test concentrations of secondary anti-TB drugs but also provide a baseline for future evaluations of M. tuberculosis AST with the more recently developed, nonradiometric broth-based culture systems.

Anti-Bacterial Agents↗
PubMed1995

The agr P2 operon: an autocatalytic sensory transduction system in Staphylococcus aureus.

The synthesis of virulence factors and other exoproteins in Staphylococcus aureus is controlled by the global regulator, agr. Expression of secreted proteins is up-regulated in the postexponential growth phase, whereas expression of surface proteins is down-regulated by agr. The agr locus consists of two divergent operons, transcribed from neighboring but non-overlapping promoters, P2 and P3. The P2 operon sequence, reported here, contains 4 open reading frames, agrA, C, D, and B, of which A and C appear to encode proteins of a classical 2-component signal transduction pathway. The P3 operon specifies a 0.5 kb transcript, RNA III, which is the actual effector of the agr response, and, incidentally, encodes the agr-regulated peptide delta-hemolysin. Transcriptional fusions have shown that both P2 and P3 are agr sensitive (function in an agr+ but not in an agr- background) and deletion analysis has shown that all four of the P2 ORFs are involved; agrA and agrC seem to be absolutely required for the transcriptional activation of the agr locus, whereas agrB and agrD seem to be partially required. Since transcription of P2 requires P2 operon products, the P2 operon is autocatalytic, and is thus admirably suited to the need for rapid production of exoproteins at a time when overall growth is coming to a halt.

Amino Acid Sequence↗
PubMed1993

Evidence for a clonal origin of methicillin resistance in Staphylococcus aureus.

Soon after methicillin was introduced into clinical practice in the early 1960s, resistant strains of Staphylococcus aureus (MRSA) appeared, bearing a newly acquired resistance gene, mecA, that encodes a penicillin binding protein, PBP2a. MRSA have spread throughout the world, and an investigation of the clonality of 472 isolates by DNA hybridization was performed. All 472 isolates could be divided into six temporally ordered mecA hybridization patterns, and three of these were subdivided by the chromomosomal transposon Tn554. Each Tn554 pattern occurred in association with one and only one mecA pattern, suggesting that mecA divergence preceded the acquisition of Tn554 in all cases and therefore that mecA may have been acquired just once by S. aureus.

Bacterial Proteins↗
PubMed1993

Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule.

The production of most toxins and other exoproteins in Staphylococcus aureus is controlled globally by a complex polycistronic regulatory locus, agr. Secretory proteins are up-regulated by agr whereas surface proteins are down-regulated. agr contains two divergent promoters, one of which directs the synthesis of a 514 nucleotide (nt) transcript, RNAIII. In this report, we show that the cloned RNAIII determinant restores both positive and negative regulatory functions of agr to an agr-null strain and that the RNA itself, rather than any protein, is the effector molecule. RNAIII acts primarily on the initiation of transcription and, secondarily in some cases, at the level of translation. In these cases, translation and transcription are regulated independently. RNAIII probably regulates translation directly by interacting with target gene transcripts and transcription indirectly by means of intermediary protein factors.

Base Sequence↗
PubMed1993

Catalase-peroxidase gene sequences in isoniazid-sensitive and -resistant strains of Mycobacterium tuberculosis from New York City.

Isoniazid resistance in Mycobacterium tuberculosis is associated with lack of catalase-peroxidase activity. A recent study showed that some isoniazid-resistant M. tuberculosis strains have a complete deletion of the gene (katG) encoding this enzyme. To examine what proportion of clinical isolates of M. tuberculosis have katG deletion, katG sequences in 80 randomly selected isolates from New York City were analyzed. Polymerase chain reaction was used to amplify a 282-bp segment of M. tuberculosis katG and showed that 35 (90%) of 39 isoniazid-sensitive and 31 (76%) of 41 isoniazid-resistant strains contained katG sequences (P > .1). Ten multidrug and high-level isoniazid-resistant strains with identical restriction fragment length polymorphism patterns were also analyzed. All were found to have katG sequences. These findings suggest that mechanisms other than complete deletion of katG are involved in isoniazid resistance among most clinical isolates of M. tuberculosis from New York City.

Base Sequence↗
PubMed1992

Regulation of the protein A-encoding gene in Staphylococcus aureus.

The synthesis of several exoproteins, including protein A (SpA) in Staphylococcus aureus is coordinately regulated by the agr locus. Different constructs of the SpA-encoding gene (spa) were introduced into Agr+ and Agr- derivatives of a spa- strain of S. aureus. Plasmid-located spa with deletions at the 3' end expressed a truncated SpA which was almost exclusively extracellular and which confirmed the role of C-terminal region X in cell-wall binding. In the Agr- host, the production of SpA was elevated severalfold. Transcriptional and translational fusions were constructed to study the agr- mediated regulation of spa gene expression. Translational fusions of a beta-lactamase (Bla)-encoding ApR reporter gene with the spa promoter and N-terminal coding sequences expressed elevated levels of Bla activity in the Agr- host. In contrast, a transcriptional fusion of the spa gene with a promoter of the positively regulated staphylococcal epidermolytic toxin A (ETA)-encoding gene synthesized higher levels of SpA in an Agr+ host, as compared to Agr-. Moreover, the synthesis of SpA in the Agr+ strain was switched on during the transition from the exponential to stationary phase in a similar fashion to ETA itself. These data strongly indicate that the regulation of both SpA and ETA occurs at the transcriptional level in S. aureus. The agr-regulated spa promoter was defined by deletion analysis and by transcript mapping.

Base Sequence↗
PubMed1991

A temporal signal, independent of agr, is required for hla but not spa transcription in Staphylococcus aureus.

Staphylococcus aureus exoprotein expression is controlled by a global regulon known as agr. This system activates transcription of some target genes and represses transcription of others. Target genes expressed postexponentially such as alpha-hemolysin (hla) are activated by agr; target genes expressed during exponential phase such as protein A (spa) are repressed by agr. A unique feature of the agr system is that this transcriptional regulation is mediated by a 517-nucleotide transcript, RNAIII. While it is clear that agr differentially regulates the expression of exponential and postexponential exoproteins, the precise role of agr in the temporal control of these events has not yet been explored. In this report, we examine the effects of expressing RNAIII, the agr regulator, under the control of the inducible beta-lactamase (bla) promoter at different times in the growth cycle. We confirm previous results showing that agr is required for postexponential-phase expression of hla and further show that a separate postexponential-phase signal independent of agr function is also needed for activation of hla transcription. We also show that in an agr mutant transcription of spa occurs throughout the growth cycle, is inhibited immediately upon induction of RNAIII, and is thus indifferent to the postexponential signal required for hla activation.

Bacterial Toxins↗
PubMed1990

Cloning and nucleotide sequence of a chromosomally encoded tetracycline resistance determinant, tetA(M), from a pathogenic, methicillin-resistant strain of Staphylococcus aureus.

This report describes the cloning and sequencing of a chromosomally encoded tetracycline resistance determinant from a clinical isolate of methicillin-resistant Staphylococcus aureus. On the basis of the sequence, the gene is in the tet(M) class, and it was shown that the S. aureus tetA(M) gene is induced at the level of transcription.

Amino Acid Sequence↗
PubMed1989

pT181 plasmid replication is regulated by a countertranscript-driven transcriptional attenuator.

pT181 is the prototype of a family of staphylococcal plasmids that regulate their replication by means of antisense RNAs (countertranscripts) that block expression of the plasmid-coded initiator protein. In this paper, we show that the pT181 countertranscripts induce premature termination (attenuation) of the initiator mRNA by promoting the formation of a termination-causing hairpin just 5' to the initiator start codon. In the absence of the countertranscripts, an upstream sequence, the preemptor, pairs with the proximal arm of the terminator hairpin, preventing termination and permitting transcription of the initiator gene. This system thus differs from the classical attenuators in that attenuation is driven by antisense RNAs rather than by tRNA-induced stalling of ribosomes.

Bacterial Proteins↗
PubMed1988

Cloning, characterization, and sequencing of an accessory gene regulator (agr) in Staphylococcus aureus.

We have previously identified a gene in Staphylococcus aureus, agr, whose activity is required for high-level post-exponential-phase expression of a series of secreted proteins. In this paper, we describe the cloning of this gene in Escherichia coli by using an inserted transposon (Tn551) as a cloning probe. The cloned gene, consisting of a 241-codon open reading frame containing the site of the transposon insertion, was recloned to an S. aureus vector, pSK265, and shown to be functional in S. aureus. Activity was evaluated by determinations of alpha-hemolysin, beta-hemolysin, and toxic shock syndrome toxin-1 production in early-stationary-phase cultures. The cloned gene showed considerable variation with respect to different exoproteins and different host strains compared with the chromosomal agr determinant; this variation could not be attributed to the higher copy number of the cloned gene and probably reflects inapparent subtleties of the regulatory system.

Amino Acid Sequence↗
PubMed1987

A site-specific recombination function in Staphylococcus aureus plasmids.

All known small staphylococcal plasmids possess one or two recombination sites at which site-specific cointegrate formation occurs. One of these sites, RSA, is present on two small multicopy plasmids, pT181 and pE194; it consists of 24 base pairs of identity in the two plasmids, the "core," flanked by some 50 base pairs of decreasing homology. Here we show that recombination at RSA is recA independent and is mediated by a plasmid-encoded, trans-acting protein, Pre (plasmid recombination). Pre-mediated recombination is site specific in that it occurs within the core sequence of RSA in a recA1 host. Recombination also occurs between two intramolecular RSA sites. Unlike site-specific recombination systems encoded by other plasmids, Pre-RSA is not involved in plasmid maintenance.

Amino Acid Sequence↗
PubMed1986

Conversion of a homogeneously methicillin-resistant strain of Staphylococcus aureus to heterogeneous resistance by Tn551-mediated insertional inactivation.

Plasmid pRN3208, thermosensitive for replication, and carrying the erythromycin transposon Tn551, was used for insertional inactivation of methicillin resistance in a highly and homogeneously resistant strain of Staphylococcus aureus. Two kinds of insertionally inactivated cells were obtained. Cultures of the major class contained highly methicillin resistant cells with a frequency of about 10(-3) to 10(-4), produced DNA with methicillin resistance transforming activity, and also produced penicillin binding protein 2a, the 78 kd low affinity penicillin binding protein characteristic of methicillin resistant Staphylococcus aureus, in apparently normal quantities. The single member of class B had no detectable methicillin resistant cells (less than 10(-8)) with an MIC greater than 1 micrograms/ml, contained no DNA with methicillin resistant transforming activity and no penicillin binding protein 2a. The data suggest that in the class A cells insertional inactivation did not affect the structural gene(s) of methicillin resistance but a regulatory locus or loci needed for the homogeneous expression of resistance.

Bacterial Proteins↗
PubMed1985

Replication control for pT181, an indirectly regulated plasmid.

PT181 is a fully sequenced Staphylococcus aureus plasmid whose size is 4,437 bp. It specifies tetracycline resistance and has a copy number of about 22 per cell in exponentially growing cultures. The functional organization of the pT181 replicon is centered around the coding sequence for a 35-kd protein, RepC, that is absolutely required for replication of the plasmid. The replication origin is contained within the repC coding sequence and the region immediately 5' to the RepC start is involved in control of the plasmid replication rate. PT181 replication is controlled at the level of RepC synthesis by a negative regulatory system that is functionally similar to that of the Co1E1 and IncFII plasmids of Escherichia coli. The pT181 control circuit involves 2 short transcripts, RNA I and RNA II, that are transcribed from the region specifying the 5' end of the untranslated repC mRNA leader and in the opposite direction. These are referred to as countertranscripts. The countertranscripts regulate RepC synthesis by a mechanism that probably involves interaction with the repC mRNA leader in a manner that interferes with translation. Both of the countertranscripts seem to be necessary for normal replication control; their separate roles remain unclear. Unlike plasmids of the Co1E1 and IncFII groups, plasmids such as Co1E1 are considered to have direct regulation of replication because the inhibitory element of the copy control circuit directly inhibits the initiation of replication. Plasmids such as pT181 are considered to have indirect regulation of replication because the product of the regulated step, RepC, is trans-active. Plasmids of the IncFII type are considered to have direct regulation of replication because the product of the regulated step, RepA is cis-active The analysis of pT181 replication physiology has illustrated 2 important differences between directly and indirectly regulated plasmids: a) for directly regulated plasmids, copy mutants specifying a normal inhibitor substance but an inactive target site exclude the wild-type or recessive mutants by directly interfering with their replication. Analogous mutants of indirectly regulated plasmids coexist readily with the wild-type and all mutants (although they do manifest segregational incompatibility) because the Rep protein is always shared by all plasmids in the cell, regardless of its source. b) Mutations of directly regulated plasmids in the region where target transcript and countertranscript overlap may give rise to totally new incompatibility groups because they engender independently self-correcting copy pools.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗