bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation of
tlyA
Confers Capreomycin Resistance in
Mycobacterium tuberculosis
Authors: Maus Courtney E. , Plikaytis Bonnie B. , Shinnick Thomas M. 
Published: January 2005

ABSTRACT

Capreomycin, an important drug for the treatment of multidrug-resistant tuberculosis, is a macrocyclic peptide antibiotic produced by
Saccharothrix mutabolis
subspecies
capreolus
. The basis of resistance to this drug was investigated by isolating and characterizing capreomycin-resistant strains of
Mycobacterium smegmatis
and
Mycobacterium tuberculosis
. Colonies resistant to capreomycin were recovered from a library of transposon-mutagenized
M. smegmatis
. The transposon insertion site of one mutant was mapped to an open reading frame in the unfinished
M. smegmatis
genome corresponding to the
tlyA
gene (Rv1694) in the
M. tuberculosis
H37Rv genome. In
M. smegmatis
spontaneous capreomycin-resistant mutants, the
tlyA
gene was disrupted by one of three different naturally occurring insertion elements. Genomic DNAs from pools of transposon mutants of
M. tuberculosis
H37Rv were screened by PCR by using primers to the
tlyA
gene and the transposon to detect mutants with an insertion in the
tlyA
gen
e
. One capreomycin-resistant mutant was recovered that contained the transposon inserted at base 644 of the
tlyA
gene. Complementation with the wild-type
tlyA
gene restored susceptibility to capreomycin in the
M. smegmatis
and
M. tuberculosis tlyA
transposon mutants. Mutations were found in the
tlyA
genes of 28 spontaneous capreomycin-resistant mutants generated from three different
M. tuberculosis
strains and in the
tlyA
genes of capreomycin-resistant clinical isolates. In in vitro transcription-translation assays, ribosomes from
tlyA
mutant but not
tlyA
+
strains resist capreomycin inhibition of transcription-translation. Therefore, TlyA appears to affect the ribosome, and mutation of
tlyA
confers capreomycin resistance.
Novel SHV-Derived Extended-Spectrum β-Lactamase, SHV-57, That Confers Resistance to Ceftazidime but Not Cefazolin
Authors: Ma Ling , Alba Jimena , Chang Feng-Yee , Ishiguro Masaji , Yamaguchi Keizo , Siu L. K. , Ishii Yoshikazu 
Published: January 2005

ABSTRACT

A new SHV-derived extended-spectrum β-lactamase, SHV-57, that confers high-level resistance to ceftazidime but not cefotaxime or cefazolin was identified from a national surveillance study conducted in Taiwan in 1998. An
Escherichia coli
isolate resistant to ampicillin, cephalothin, and ceftazidime but sensitive to cefoxitin, ceftriaxone, cefotaxime, imipenem, and a narrow-spectrum cephem (cefazolin) was isolated from the urine of a patient treated with β-lactam antibiotics. Resistance to β-lactams was conjugatively transferred with a plasmid of about 50 kbp. The pI of this enzyme was 8.3. The sequence of the gene was determined, and the open reading frame of the gene was found to consist of 861 bases (GenBank accession number
AY223863
). Kinetic parameters showed that SHV-57 had a poor affinity to cefazolin. The

K
m

value toward cefazolin (5.57 × 10
3
μM) was extremely high in comparison to those toward ceftazidime (30.9 μM) and penicillin G (67 μM), indicating its low affinity to cefazolin. Although the

K
m

value of the β-lactamase inhibitor was too high for the study of catalytic activity (
k
cat
), indicating the low
k
cat
of SHV-57, the SHV-57 carrier was highly susceptible to a β-lactam-β-lactamase inhibitor combination. Comparison of the three-dimensional molecular model of SHV-57 with that of the SHV-1 β-lactamase suggests that the substitution of arginine for leucine-169 in the Ω loop is important for the substrate specificity.
Incidence and Mechanism of Ciprofloxacin Resistance in
Campylobacter
spp. Isolated from Commercial Poultry Flocks in the United Kingdom before, during, and after Fluoroquinolone Treatment
Authors: Griggs Deborah J. , Johnson Maggie M. , Frost Jennifer A. , Humphrey Tom , Jørgensen Frieda , Piddock Laura J. V. 
Published: January 2005

ABSTRACT

Five commercial broiler flocks were treated with a fluoroquinolone for a clinically relevant infection. Fresh feces from individual chickens and environmental samples were cultured for campylobacters before, during, and weekly posttreatment until slaughter. Both
Campylobacter jejuni
and
C. coli
were isolated during all treatment phases. An increased proportion of quinolone-resistant strains was seen during treatment, and these strains persisted posttreatment. One quinolone-resistant isolate of each species, each serotype, and each phage type from each sample at all treatment phases was examined for its phenotype and mechanism of resistance. Two resistant phenotypes were isolated: Nal
r
Cip
r
and Nal
r
Cip
s
. The majority (269 of 290) of fluoroquinolone-resistant isolates, whether they were
C. jejuni
or
C. coli
, had a mutation in
gyrA
that resulted in the substitution Thr-86→Ile. The other
gyrA
mutations detected were Thr-86→Ala (
n
= 17) and Asp-90→Asn (
n
= 10). The genotypic variation, based on the silent mutations in
gyrA
identified by the denaturing high-performance liquid chromatography pattern and DNA sequencing, was used to supplement typing data and provided evidence for both the spread of preexisting resistant strains and the selection of spontaneous resistant mutants in treated flocks. Multidrug resistance was significantly (
P
< 0.01) associated with resistance to ciprofloxacin. Twenty-five percent (73 of 290) of ciprofloxacin-resistant isolates but only 13% (24 of 179) of susceptible isolates were resistant to three or more unrelated antimicrobial agents. In conclusion, quinolone-resistant campylobacters were isolated from commercial chicken flocks in high numbers following therapy with a veterinary fluoroquinolone. Most ciprofloxacin-resistant isolates had the GyrA substitution Thr-86→Ile. Resistant isolates were isolated from the feces of some flocks up to the point of slaughter, which may have consequences for public health.
Rapid Diffusion of Fluorescent Tracers into
Staphylococcus epidermidis
Biofilms Visualized by Time Lapse Microscopy
Authors: Rani Suriani Abdul , Pitts Betsey , Stewart Philip S. 
Published: January 2005

ABSTRACT

The transient diffusion of fluorescent tracers into biofilm cell clusters of
Staphylococcus epidermidis
was visualized by time lapse confocal scanning laser microscopy. Rhodamine B diffused into the center of cell clusters that were 200 to 600 μm in diameter within a few minutes. The apparent effective diffusion coefficient calculated from these data averaged 3.7 × 10
−7
cm
2
s
−1
or 11% of the value in pure water. Fluorescein diffused into biofilm more rapidly, with a diffusion coefficient that averaged 1.6 × 10
−6
cm
2
s
−1
, or 32% of the value in water. This study provides direct, visual confirmation that solutes the size of many antibiotics and biocides can diffuse rapidly into biofilms.
Discovering the Mechanism of Action of Novel Antibacterial Agents through Transcriptional Profiling of Conditional Mutants
Authors: Freiberg C. , Fischer H. P. , Brunner N. A. 
Published: January 2005

ABSTRACT

We present a new strategy for predicting novel antibiotic mechanisms of action based on the analysis of whole-genome microarray data. We first built up a reference compendium of
Bacillus subtilis
expression profiles induced by 14 different antibiotics. This data set was expanded by adding expression profiles from mutants that showed downregulation of genes coding for proven or emerging antibacterial targets. Here, we investigate conditional mutants underexpressing
ileS
,
pheST
,
fabF
, and
accDA
, each of which is essential for growth. Our proof-of-principle analyses reveal that conditional mutants can be used to mimic chemical inhibition of the corresponding gene products. Moreover, we show that a statistical data analysis combined with thorough pathway and regulon analysis can pinpoint the molecular target of uncharacterized antibiotics. We apply this approach to two novel antibiotics: a recently published phenyl-thiazolylurea derivative and the natural product moiramide B. Our results support recent findings suggesting that the phenyl-thiazolylurea derivative is a novel phenylalanyl-tRNA synthetase inhibitor. Finally, we propose a completely novel antibiotic mechanism of action for moiramide B based on inhibition of the bacterial acetyl coenzyme A carboxylase.
Bloodstream Infections Caused by Antibiotic-Resistant Gram-Negative Bacilli: Risk Factors for Mortality and Impact of Inappropriate Initial Antimicrobial Therapy on Outcome
Authors: Kang Cheol-In , Kim Sung-Han , Park Wan Beom , Lee Ki-Deok , Kim Hong-Bin , Kim Eui-Chong , Oh Myoung-don , Choe Kang-Won 
Published: January 2005

ABSTRACT

The marked increase in the incidence of infections due to antibiotic-resistant gram-negative bacilli in recent years is of great concern, as patients infected by those isolates might initially receive antibiotics that are inactive against the responsible pathogens. To evaluate the effect of inappropriate initial antimicrobial therapy on survival, a total of 286 patients with antibiotic-resistant gram-negative bacteremia, 61 patients with
Escherichia coli
bacteremia, 65 with
Klebsiella pneumoniae
bacteremia, 74 with
Pseudomonas aeruginosa
bacteremia, and 86 with
Enterobacter
bacteremia, were analyzed retrospectively. If a patient received at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture collection, the initial antimicrobial therapy was considered to have been appropriate. High-risk sources of bacteremia were defined as the lung, peritoneum, or an unknown source. The main outcome measure was 30-day mortality. Of the 286 patients, 135 (47.2%) received appropriate initial empirical antimicrobial therapy, and the remaining 151 (52.8%) patients received inappropriate therapy. The adequately treated group had a 27.4% mortality rate, whereas the inadequately treated group had a 38.4% mortality rate (
P
= 0.049). Multivariate analysis showed that the significant independent risk factors of mortality were presentation with septic shock, a high-risk source of bacteremia,
P. aeruginosa
infection, and an increasing APACHE II score. In the subgroup of patients (
n
= 132) with a high-risk source of bacteremia, inappropriate initial antimicrobial therapy was independently associated with increased mortality (odds ratio, 3.64; 95% confidence interval, 1.13 to 11.72;
P
= 0.030). Our data suggest that inappropriate initial antimicrobial therapy is associated with adverse outcome in antibiotic-resistant gram-negative bacteremia, particularly in patients with a high-risk source of bacteremia.
Antimicrobial Susceptibility Survey of
Streptococcus pyogenes
Isolated in Japan from Patients with Severe Invasive Group A Streptococcal Infections
Authors: Ikebe Tadayoshi , Hirasawa Kyoko , Suzuki Rieko , Isobe Junko , Tanaka Daisuke , Katsukawa Chihiro , Kawahara Ryuji , Tomita Masaaki , Ogata Kikuyo , Endoh Miyoko , Okuno Rumi , Watanabe Haruo 
Published: January 2005

ABSTRACT

We assessed antimicrobial susceptibility against 211
Streptococcus pyogenes
strains isolated from patients with severe invasive group A streptococcal infections. Overall, 3.8, 1.4, 1.4, and 0.5% of the isolates were resistant to erythromycin, clindamycin, telithromycin, and ciprofloxacin, respectively, and 10.4% had intermediate resistance to ciprofloxacin. All isolates were susceptible to ampicillin and cefotaxime.
AcrAB Efflux Pump Plays a Role in Decreased Susceptibility to Tigecycline in
Morganella morganii
Authors: Ruzin Alexey , Keeney David , Bradford Patricia A. 
Published: January 2005

ABSTRACT

Transposon mutagenesis of a clinical isolate of
Morganella morganii
, G1492 (tigecycline MIC of 4 μg/ml), yielded two insertion knockout mutants for which tigecycline MICs were 0.03 μg/ml. Transposon insertions mapped to
acrA
, which is constitutively overexpressed in G1492, suggesting a role of the AcrAB efflux pump in decreased susceptibility to tigecycline in
M. morganii
.
Test Characteristics of Perirectal and Rectal Swab Compared to Stool Sample for Detection of Fluoroquinolone-Resistant
Escherichia coli
in the Gastrointestinal Tract
Authors: Lautenbach Ebbing , Harris Anthony D. , Perencevich Eli N. , Nachamkin Irving , Tolomeo Pam , Metlay Joshua P. 
Published: January 2005

ABSTRACT

Among 63 patients enrolled in a prospective cohort study of gut colonization with fluoroquinolone-resistant
Escherichia coli
, the sensitivity of perirectal swab compared to stool sample was 90% (95% confidence interval [CI], 70 to 99%) and the specificity was 100% (95% CI, 91 to 100%). For rectal swab, the sensitivity was 90% (95% CI, 68 to 99%) and the specificity was 100% (95% CI, 91 to 100%).
Cloning of a Novel Gene for Quinolone Resistance from a Transferable Plasmid in
Shigella flexneri
2b
Authors: Hata Mami , Suzuki Masahiro , Matsumoto Masakado , Takahashi Masao , Sato Katsuhiko , Ibe Shiro , Sakae Kenji 
Published: January 2005

ABSTRACT

A novel gene for quinolone resistance was cloned from a transferable plasmid carried by a clinical isolate of
Shigella flexneri
2b that was resistant to fluoroquinolones. The plasmid conferred low-level resistance to quinolones on
Escherichia coli
HB101. The protein encoded by the gene showed 59% amino acid identity with Qnr.
Florfenicol-Chloramphenicol Exporter Gene
fexA
Is Part of the Novel Transposon Tn
558
Authors: Kehrenberg Corinna , Schwarz Stefan 
Published: January 2005

ABSTRACT

The florfenicol-chloramphenicol exporter gene
fexA
is part of the novel transposon Tn
558
from
Staphylococcus lentus.
Similarities between Tn
558
and Tn
554
from
Staphylococcus aureus
included the arrangement of the transposase genes
tnpA
to -
C
and an
att554
-like target sequence. Circular forms of Tn
558
were detected and suggest the functional activity of this transposon.
In Vitro Activity of Telithromycin against Viridans Group Streptococci and
Streptococcus bovis
Isolated from Blood: Antimicrobial Susceptibility Patterns in Different Groups of Species
Authors: Rodríguez-Avial Iciar , Rodríguez-Avial Carmen , Culebras Esther , Picazo Juan J. 
Published: January 2005

ABSTRACT

The in vitro activities of penicillin, erythromycin, clindamycin, and telithromycin were determined against 155 viridans group streptococci (VGS) and 18
Streptococcus bovis
blood isolates. Heterogeneity in the susceptibility patterns and macrolide resistance phenotypes and genotypes in the different groups of VGS was detected. We found seven telithromycin-resistant
S. bovis
isolates all harboring the
erm
(B) gene.
Extended-Spectrum β-Lactamases in
Escherichia coli
Isolated from Dogs and Cats in Rome, Italy, from 2001 to 2003
Authors: Carattoli Alessandra , Lovari Sarah , Franco Alessia , Cordaro Gessica , Di Matteo Paola , Battisti Antonio 
Published: January 2005

ABSTRACT

We report expanded-spectrum cephalosporin resistance in
Escherichia coli
from dogs and cats in Rome, Italy. Three major β-lactamases (CMY-2, SHV-12, and CTX-M-1) are reported for the first time in
E. coli
from sick and healthy dogs and cats. Molecular characterization suggests the presence of several combinations of β-lactamase genes in
E. coli
from companion animals.
ACM SIGACT news distributed computing column 15
Authors: Rajsbaum Sergio 
Published: January 2005

The Distributed Computing Column covers the theory of systems that are composed of a number of interacting computing elements. These include problems of communication and networking, databases, distributed shared memory, multiprocessor architectures, operating systems, verification, Internet, and the Web.
This issue contains two items:
• An eulogy in memory of Shimon Even, who passed away on May 1st, 2004. He was a highly influential educator, and played a major role in establishing computer science education in Israel. He did pioneering work in various areas, including parallel and distributed computing. As Oded Goldreich says in his PODC 2004 proceedings eulogy, Shimon Even was a great scientist and a remarkable person. His attitudes toward research have influenced anybody who was fortunate to have an interaction with him, he always followed his own judgment and understanding, rather than the common trend or fashion. He sought simple solutions that uncover the essence of the problem. He spent much time seeking the best way to present his own work as well as the work of others in lectures and writing. This quote comes to mind, about having found a good problem to work on.
<i>Not that I quite know indeed what situations the seeking fabulist does "find"; he seeks them enough assuredly, but he discoveries are, like those of the navigator, the chemist, the biologist, scarce more than alert recognitions. He comes upon the interesting thing as Columbus came upon the isle of San Salvador, because he had moved in the right direction for it---also because he knew, with the encounter, what "making land" then and there represented.</i>
Henry James
• The 2004 Gödel Prize is great news for the distributed computing community: it is shared between two journal papers that discovered a fundamental relation between distributed computing and topology, by Maurice Herlihy and Nir Shavit, and Michael Saks and Fotios Zaharoglou. To celebrate this, I am happy to present personal perspectives by the authors of these papers, and by Elizabeth Borowsky and Eli Gafni, that coauthored a third paper with the discovery, but only in a conference and hence not eligible for the prize. I include perspectives also by other people that produced seminal work on the same subject: Soma Chaudhuri and Shlomo Moran.
The DISC conference is collocated this year with GETCO, a workshop on topological methods in concurrency and distributed computing. They will dedicate a joint session to celebrate the prize.
Many thanks to the contributors of this issue.
Safe compositional specification of networking systems
Authors: Bestavros Azer , Bradley Adam , Kfoury Assaf , Matta Ibrahim 
Published: January 2005

The <i>science</i> of network service composition has emerged as one of the grand themes of networking research [17] as a direct result of the complexity and sophistication of emerging networked systems and applications. By "service composition" we mean that the performance and correctness properties local to the various constituent components of a service can be readily composed into global (end-to-end) properties without re-analyzing any of the constituent components in isolation, or as part of the whole composite service. The set of laws that govern such composition is what will constitute that new science of composition.
The heterogeneity and open nature of network systems make composition quite challenging, and thus programming network services has been largely inaccessible to the average user. We identify (and outline) a research agenda in which we aim to develop a <i>specification language</i> that is expressive enough to describe different components of a network service, and that will include <i>type hierarchies</i> inspired by type systems in general programming languages that enable the safe composition of software components. We envision this new science of composition to be built upon several theories, possibly including control theory, network calculus, scheduling theory, and game theory. In essence, different theories may provide different <i>languages</i> by which certain properties of system components can be expressed and composed into larger systems. We then seek to lift these lower-level specifications to a higher level by abstracting away details that are irrelevant for safe composition at the higher level, thus making theories scalable and useful to the average user. In this paper we focus on services built upon an overlay traffic management architecture, and we use control theory and QoS theory as example theories from which we lift up compositional specifications.
Efficient incremental algorithms for dynamic detection of likely invariants
Authors: Perkins Jeff H. , Ernst Michael D. 
Published: January 2005

Dynamic detection of likely invariants is a program analysis that generalizes over observed values to hypothesize program properties. The reported program properties are a set of likely invariants over the program, also known as an operational abstraction. Operational abstractions are useful in testing, verification, bug detection, refactoring, comparing behavior, and many other tasks.
Previous techniques for dynamic invariant detection scale poorly or report too few properties. Incremental algorithms are attractive because they process each observed value only once and thus scale well with data sizes. Previous incremental algorithms only checked and reported a small number of properties. This paper takes steps toward correcting this problem. The paper presents two new incremental algorithms for invariant detection and compares them analytically and experimentally to two existing algorithms. Furthermore, the paper presents four optimizations and shows how to implement them in the context of incremental algorithms. The result is more scalable invariant detection that does not sacrifice functionality.
PSE
Authors: Manevich Roman , Sridharan Manu , Adams Stephen , Das Manuvir , Yang Zhe 
Published: January 2005

In this paper, we describe PSE (Postmortem Symbolic Evaluation), a static analysis algorithm that can be used by programmers to diagnose software failures. The algorithm requires minimal information about a failure, namely its kind (e.g. NULL dereference), and its location in the program's source code. It produces a set of execution traces along which the program can be driven to the given failure.
PSE tracks the flow of a single value of interest from the point in the program where the failure occurred back to the points in the program where the value may have originated. The algorithm combines a novel dataflow analysis and memory alias analysis in a manner that allows for precise exploration of the program's behavior in polynomial time.
We have applied PSE to the problem of diagnosing potential NULL-dereference errors in a suite of C programs, including several SPEC benchmarks and a large commercial operating system. In most cases, the analysis is able to either validate a pointer dereference, or find precise error traces demonstrating a NULL value for the pointer, in less than a second.
Back to direct style II
Authors: Danvy Olivier , Lawall Julia L. 
Published: January 2005

We continue to investigate the direct-style transformation by extending it to programs requiring
call-with-current-continuation
(a.k.a.
call/cc
). The direct style (DS) and the continuation-passing style (CPS) transformations form a Galois connection. This pair of functions has a place in the programmer's toolbox—yet we are not aware of the existence of any other DS transformer.

Starting from our DS transformer towards pure, call-by-value functional terms (Scheme), we extend it with a counting analysis to detect non-canonical occurrences of a continuation. The declaration of such a continuation is translated into a
call/cc
and its application into the application of the corresponding first-class continuation

We also present staged versions of the DS and of the CPS transformations, where administrative reductions are separated from the actual translation, and where the actual translations are carried out by local, structure-preserving rewriting rules. These staged transformations are used to prove the Galois continuation.
Together, the CPS and the DS transformations enlarge the class of programs that can be manipulated on a semantic basis. We illustrate this point with partial evaluation, by specializing a Scheme program with respect to a static part of its input. The program uses coroutines. This illustration achieves a first: a static coroutine is executed statically and its computational content is inlined in the residual program.