bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chitosan Augments Photodynamic Inactivation of Gram-Positive and Gram-Negative Bacteria
Authors: Tsai Tsuimin , Chien Hsiung-Fei , Wang Tze-Hsien , Huang Ching-Tsan , Ker Yaw-Bee , Chen Chin-Tin 
Published: February 2011

ABSTRACT

Antimicrobial photodynamic inactivation (PDI) was shown to be a promising treatment modality for microbial infections. This study explores the effect of chitosan, a polycationic biopolymer, in increasing the PDI efficacy against Gram-positive bacteria, including
Staphylococcus aureus
,
Staphylococcus epidermidis
,
Streptococcus pyogenes
, and methicillin-resistant
S. aureus
(MRSA), as well as the Gram-negative bacteria
Pseudomonas aeruginosa
and
Acinetobacter baumannii
. Chitosan at <0.1% was included in the antibacterial process either by coincubation with hematoporphyrin (Hp) and subjection to light exposure to induce the PDI effect or by addition after PDI and further incubation for 30 min. Under conditions in which Hp-PDI killed the microbe on a 2- to 4-log scale, treatment with chitosan at concentrations of as low as 0.025% for a further 30 min completely eradicated the bacteria (which were originally at ∼10
8
CFU/ml). Similar results were also found with toluidine blue O (TBO)-mediated PDI in planktonic and biofilm cells. However, without PDI treatment, chitosan alone did not exert significant antimicrobial activity with 30 min of incubation, suggesting that the potentiated effect of chitosan worked after the bacterial damage induced by PDI. Further studies indicated that the potentiated PDI effect of chitosan was related to the level of PDI damage and the deacetylation level of the chitosan. These results indicate that the combination of PDI and chitosan is quite promising for eradicating microbial infections.
Lacticin Q-Mediated Selective Toxicity Depending on Physicochemical Features of Membrane Components
Authors: Yoneyama Fuminori , Ohno Kanako , Imura Yuichi , Li Mengqi , Zendo Takeshi , Nakayama Jiro , Matsuzaki Katsumi , Sonomoto Kenji 
Published: February 2011

ABSTRACT
Lacticin Q, a lactococcal pore-forming bacteriocin, shows activity toward Gram-positive bacteria but not Gram-negative bacteria. Lacticin Q did not induce permeability of the outer membrane of Gram-negative bacteria. Experiments using model membranes containing outer membrane components suggested that lacticin Q binds to the outer membrane of Gram-negative bacteria but is unable to penetrate it. The lack of activity of lacticin Q was attributed to physicochemical features of the outer membrane components.
In Vivo
Efficacy of the Novel Aminoglycoside ACHN-490 in Murine Infection Models
Authors: Reyes Noe , Aggen James B. , Kostrub Corwin F. 
Published: February 2011

ABSTRACT

Aminoglycosides are broad-spectrum antibiotics with particular clinical utility against life-threatening infections. As resistance to antibiotics, including aminoglycosides, continues to grow, there is a need for new and effective antimicrobial agents. ACHN-490 is a novel aminoglycoside in clinical development with activity against multidrug-resistant Gram-negative and select Gram-positive pathogens. Here we assess the
in vivo
efficacy of ACHN-490 against a variety of common pathogens in two murine models: the septicemia and neutropenic thigh models. When its activity against a gentamicin-susceptible strain of
Escherichia coli
was tested in the septicemia model, ACHN-490 improved 7-day survival with a dose-response profile similar to that of gentamicin, with 100% survival seen at doses of 1.6 mg/kg of body weight and above. In animals infected with a gentamicin-susceptible strain of
Pseudomonas aeruginosa
, treatment with either ACHN-490 or gentamicin led to 100% survival at doses of 16 mg/kg and above in the septicemia model. ACHN-490 was also effective in the neutropenic thigh model, reducing multidrug-resistant
Enterobacteriaceae
family and methicillin-resistant
Staphylococcus aureus
strains, as well as broadly susceptible strains, to static levels with dose-dependent activity. Against gentamicin-sensitive
Enterobacteriaceae
and methicillin-resistant
S. aureus
, the efficacy of ACHN-490 was comparable to that of gentamicin. However, gentamicin-resistant
Enterobacteriaceae
strains and those harboring the
Klebsiella pneumoniae
carbapenemase responded to ACHN-490 but not gentamicin, with static doses ranging from 12 mg/kg to 64 mg/kg for ACHN-490. These results suggest that ACHN-490 has the potential to become a clinically useful agent against drug-resistant pathogens, including
Enterobacteriaceae
,
P. aeruginosa
, and methicillin-resistant
S. aureus
, and support further development of this promising novel aminoglycoside.
C-Terminal Amino Acids of Alpha-Melanocyte-Stimulating Hormone Are Requisite for Its Antibacterial Activity against Staphylococcus aureus
Authors: Singh Madhuri , Mukhopadhyay Kasturi 
Published: February 2011

ABSTRACTAlpha-melanocyte-stimulating hormone (α-MSH) is an endogenous neuropeptide that is known for its anti-inflammatory and antipyretic activities. We recently demonstrated that α-MSH possesses staphylocidal activity and causes bacterial membrane damage. To understand the role of its amino acid sequences in the staphylocidal mechanism, in the present study we investigated the antimicrobial activities of different fragments of α-MSH, i.e., α-MSH(6-13), α-MSH(11-13), and α-MSH(1-5), and compared them with that of the entire peptide. Our results showed that peptides containing the C-terminal region of α-MSH, namely, α-MSH(6-13) and α-MSH(11-13), efficiently killed >90% of both methicillin-sensitive and -resistantStaphylococcus aureuscells in the micromolar range and ∼50% of these cells in the nanomolar range; their efficiency was comparable to that of the entire α-MSH, whereas the peptide containing the N-terminal region, α-MSH(1-5), was found to be ineffective againstS. aureus. The antimicrobial activity of α-MSH and its C-terminal fragments was not affected by the presence of NaCl or even divalent cations such as Ca2+and Mg2+. Similar to the case for the parent peptide, α-MSH(6-13) and α-MSH(11-13) also depolarized and permeabilizedStaphylococcuscells (∼70 to 80% of the cells were depolarized and lysed after 2 h of peptide exposure at micromolar concentrations). Furthermore, scanning and transmission electron microscopy showed remarkable morphological and ultrastructural changes onS. aureuscell surface due to exposure to α-MSH-based peptides. Thus, our observations indicate that C-terminal fragments of α-MSH retain the antimicrobial activity of entire peptide and that their mechanism of action is similar to that of full-length peptide. These observations are important and are critical in the rational design of α-MSH-based therapeutics with optimal efficacy.
Deciphering the Mode of Action of the Synthetic Antimicrobial Peptide Bac8c
Authors: Spindler E. C. , Hale J. D. F. , Giddings T. H. , Hancock R. E. W. , Gill R. T. 
Published: February 2011

ABSTRACT

Bac8c (RIWVIWRR-NH
2
) is an 8-amino-acid peptide derived from Bac2A (RLARIVVIRVAR-NH
2
), a C3A/C11A variant of the naturally occurring bovine peptide, bactenecin (also known as bovine dodecapeptide), the smallest peptide with activity against a range of pathogenic Gram-positive and Gram-negative bacteria, as well as yeast. The effects of Bac8c on
Escherichia coli
were examined by studying its bacteriostatic and bactericidal properties, demonstrating its effects on proton motive force generation, and visually analyzing (via transmission electron microscopy) its effects on cells at different concentrations, in order to probe the complexities of the mechanism of action of Bac8c. Results were consistent with a two-stage model for the Bac8c mode of action. At sublethal concentrations (3 μg/ml), Bac8c addition resulted in transient membrane destabilization and metabolic imbalances, which appeared to be linked to inhibition of respiratory function. Although sublethal concentrations resulted in deleterious downstream events, such as methylglyoxal formation and free radical generation, native
E. coli
defense systems were sufficient for full recovery within 2 h. In contrast, at the minimal bactericidal concentration (6 μg/ml), Bac8c substantially but incompletely depolarized the cytoplasmic membrane within 5 min and disrupted electron transport, which in turn resulted in partial membrane permeabilization and cell death.
Differential Phenotypic and Genotypic Characteristics of
qnrS1
-Harboring Plasmids Carried by Hospital and Community Commensal Enterobacteria
Authors: Vien Le Thi Minh , AbuOun Manal , Morrison Victoria , Thomson Nicholas , Campbell James I. , Woodward Martin J. , Van Vinh Chau Nguyen , Farrar Jeremy , Schultsz Constance , Baker Stephen 
Published: February 2011

ABSTRACT

The
qnrS1
gene induces reduced susceptibility to fluoroquinolones in enterobacteria. We investigated the structure, antimicrobial susceptibility phenotype, and antimicrobial resistance gene characteristics of
qnrS1
plasmids from hospitalized patients and community controls in southern Vietnam. We found that the antimicrobial susceptibilities, resistance gene characteristics, and plasmid structures of
qnrS1
plasmids from the hospital differed from those from the community. Our data imply that the characteristics of the two plasmid groups are indicative of distinct selective pressures in the differing environments.
In Vitro
Pharmacodynamics of Simulated Pulmonary Exposures of Tigecycline Alone and in Combination against
Klebsiella pneumoniae
Isolates Producing a KPC Carbapenemase
Authors: Wiskirchen Dora E. , Koomanachai Pornpan , Nicasio Anthony M. , Nicolau David P. , Kuti Joseph L. 
Published: February 2011

ABSTRACT

Multidrug-resistant
Klebsiella pneumoniae
strains that produce a serine carbapenemase (KPC) are emerging worldwide, with few therapeutic options that retain consistent susceptibility. The objective of this study was to determine the effect of combination therapy with tigecycline versus tigecycline alone against KPC-producing isolates (KPC isolates). An
in vitro
pharmacodynamic model was used to simulate adult steady-state epithelial lining fluid concentrations of tigecycline (50 mg every 12 h) given alone and in combination with either meropenem (2 g by 3-hour infusion every 8 h) or rifampin (600 mg every 12 h). Five KPC isolates with various phenotypic profiles were exposed over 48 h. Time-kill curves were constructed, and the areas under the bacterial killing and regrowth curves (AUBCs) were calculated. No regimens tested were able to maintain bactericidal reductions in CFU over 48 h. The AUBCs for tigecycline and meropenem monotherapies at 48 h ranged from 375.37 to 388.11 and from 348.62 to 383.83 (CFU-h/ml), respectively. The combination of tigecycline plus meropenem significantly reduced the AUBCs at 24 and 48 h for isolates with tigecycline MICs of ≤2 μg/ml and meropenem MICs of ≤16 μg/ml (
P
< 0.001) but added no additional activity when the meropenem MIC was 64 μg/ml (
P
= 0.5). Rifampin provided no additional reduction in CFU or AUBC over tigecycline alone (
P
= 0.837). The combination of tigecycline with high-dose, prolonged-infusion meropenem warrants further study as a potential treatment option for these multidrug-resistant organisms.
Klebsiella pneumoniae
Outer Membrane Porins OmpK35 and OmpK36 Play Roles in both Antimicrobial Resistance and Virulence
Authors: Tsai Yu-Kuo , Fung Chang-Phone , Lin Jung-Chung , Chen Jiun-Han , Chang Feng-Yee , Chen Te-Li , Siu L. Kristopher 
Published: February 2011

ABSTRACT

OmpK35 and OmpK36 are the major outer membrane porins of
Klebsiella pneumoniae
. In this study, a virulent clinical isolate was selected to study the role of these two porins in antimicrobial resistance and virulence. The single deletion of
ompK36
(Δ
ompK36
) resulted in MIC shifts of cefazolin, cephalothin, and cefoxitin from susceptible to resistant, while the single deletion of
ompK35
(Δ
ompK35
) had no significant effect. A double deletion of
ompK35
and
ompK36
(Δ
ompK35/36
) further increased these MICs to high-level resistance and led to 8- and 16-fold increases in the MICs of meropenem and cefepime, respectively. In contrast to the routine testing medium, which is of high osmolarity, susceptibility tests using low-osmolarity medium showed that the Δ
ompK35
mutation resulted in a significant (≥4-fold) increase in the MICs of cefazolin and ceftazidime, whereas a Δ
ompK36
deletion conferred a significantly (4-fold) lower increase in the MIC of cefazolin. In the virulence assays, a significant (
P
< 0.05) defect in the growth rate was found only in the Δ
ompK35/36
mutant, indicating the effect on metabolic fitness. A significant (
P
< 0.05) increase in susceptibility to neutrophil phagocytosis was observed in both Δ
ompK36
and Δ
ompK35/36
mutants. In a mouse peritonitis model, the Δ
ompK35
mutant showed no change in virulence, and the Δ
ompK36
mutant exhibited significantly (
P
< 0.01) lower virulence, whereas the Δ
ompK35/36
mutant presented the highest 50% lethal dose of these strains. In conclusion, porin deficiency in
K. pneumoniae
could increase antimicrobial resistance but decrease virulence at the same time.
Predicting
In Vitro
Antibacterial Efficacy across Experimental Designs with a Semimechanistic Pharmacokinetic-Pharmacodynamic Model
Authors: Nielsen Elisabet I. , Cars Otto , Friberg Lena E. 
Published: February 2011

ABSTRACT

We have previously described a general semimechanistic pharmacokinetic-pharmacodynamic (PKPD) model that successfully characterized the time course of antibacterial effects seen in bacterial cultures when exposed to static concentrations of five antibacterial agents of different classes. In this PKPD model, the total bacterial population was divided into two subpopulations, one growing drug-susceptible population and one resting drug-insensitive population. The drug effect was included as an increase in the killing rate of the drug-susceptible bacteria with a maximum-effect (
E
max
) model. The aim of the present study was to evaluate the ability of this PKPD model to describe and predict data from
in vitro
experiments with dynamic concentration-time profiles. Dynamic time-kill curve experiments were performed by using an
in vitro
kinetic system, where cultures of
Streptococcus pyogenes
were exposed to benzylpenicillin, cefuroxime, erythromycin, moxifloxacin, or vancomycin using different starting concentrations (2 and 16 times the MIC) and elimination conditions (human half-life, reduced half-life, and constant concentrations). The PKPD model was applied, and the observations for the static as well as dynamic experiments were compared to model predictions based on parameter estimation using (i) static data, (ii) dynamic data, and (iii) combined static and dynamic data. Differences in experimental settings between static and dynamic experiments did not affect the growth kinetics of the bacteria significantly. With parameter reestimation, the structure of our previously proposed PKPD model could well characterize the bacterial growth and killing kinetics when exposed to dynamic concentrations with different elimination rates of all five investigated antibiotics. Furthermore, the model with parameter estimates based on data from only the static time-kill curve experiments could predict the majority of the time-kill curves from the dynamic experiments reasonably well. Adding data from dynamic experiments in the estimation improved the model fit for cefuroxime and vancomycin, indicating some differences in sensitivity to experimental conditions among the antibiotics studied.
Activity of ACHN-490 Tested Alone and in Combination with Other Agents against Pseudomonas aeruginosa
Authors: Pankuch Glenn A. , Lin Gengrong , Kubo Aya , Armstrong Eliana S. , Appelbaum Peter C. , Kosowska-Shick Klaudia 
Published: February 2011

ABSTRACT

ACHN-490 was tested alone and in combination with cefepime, doripenem, imipenem, or piperacillin-tazobactam in a synergy time-kill analysis against 25
Pseudomonas aeruginosa
strains with different resistance phenotypes. Each combination was synergistic against most isolates at 24 h, and antagonism was not observed. Combinations of ACHN-490 with cefepime, doripenem, imipenem, or piperacillin-tazobactam yielded synergies in ≥70% and ≥80% of strains at 6 and 12 h, respectively, and in ≥68% at 24 h.
Multilaboratory Testing of Two-Drug Combinations of Antifungals against
Candida albicans
,
Candida glabrata
, and
Candida parapsilosis
Authors: Chaturvedi Vishnu , Ramani Rama , Andes David , Diekema Daniel J. , Pfaller Michael A. , Ghannoum Mahmoud A. , Knapp Cindy , Lockhart Shawn R. , Ostrosky-Zeichner Luis , Walsh Thomas J. , Marchillo Karen , Messer Shawn , Welshenbaugh Amanda R. , Bastulli Cara , Iqbal Noreen , Paetznick Victor L. , Rodriguez Jose , Sein Tin 
Published: February 2011

ABSTRACT

There are few multilaboratory studies of antifungal combination testing to suggest a format for use in clinical laboratories. In the present study, eight laboratories tested quality control (QC) strain
Candida parapsilosis
ATCC 22019 and clinical isolates
Candida albicans
20533.043,
C. albicans
20464.007,
Candida glabrata
20205.075, and
C. parapsilosis
20580.070. The clinical isolates had relatively high azole and echinocandin MICs. A modified CLSI M27-A3 protocol was used, with 96-well custom-made plates containing checkerboard pairwise combinations of amphotericin B (AMB), anidulafungin (AND), caspofungin (CSP), micafungin (MCF), posaconazole (PSC), and voriconazole (VRC). The endpoints were scored visually and on a spectrophotometer or enzyme-linked immunosorbent assay (ELISA) reader for 50% growth reduction (50% inhibitory concentration [IC
50
]). Combination IC
50
s were used to calculate summation fractional inhibitory concentration indices (FICIs) (ΣFIC) based on the Lowe additivity formula. The results revealed that the IC
50
s of all drug combinations were lower or equal to the IC
50
of individual drugs in the combination. A majority of the ΣFIC values were indifferent (ΣFIC = 0.51 to 2.0), but no antagonism was observed (ΣFIC ≥ 4). Synergistic combinations (ΣFIC ≤ 0.5) were found for AMB-PSC against
C. glabrata
and for AMB-AND and AMB-CSP against
C. parapsilosis
by both visual and spectrophotometric readings. Additional synergistic interactions were revealed by either of the two endpoints for AMB-AND, AMB-CSP, AMB-MCF, AMB-PSC, AMB-VRC, AND-PSC, CSP-MCF, and CSP-PSC. The percent agreements among participating laboratories ranged from 37.5% (lowest) for AND-CSP and POS-VOR to 87.5% (highest) for AMB-MCF and AND-CSP. Median ΣFIC values showed a wide dispersion, and interlaboratory agreements were less than 85% in most instances. Additional studies are needed to improve the interlaboratory reproducibility of antifungal combination testing.
Activity of the Fluoroquinolone DC-159a in the Initial and Continuation Phases of Treatment of Murine Tuberculosis
Authors: Ahmad Zahoor , Minkowski Austin , Peloquin Charles A. , Williams Kathy N. , Mdluli Khisimuzi E. , Grosset Jacques H. , Nuermberger Eric L. 
Published: February 2011

ABSTRACT

DC-159a is a new fluoroquinolone with more potent
in vitro
activity than available fluoroquinolones against both drug-susceptible and fluoroquinolone-resistant
Mycobacterium tuberculosis
. Here, we report that DC-159a displays pharmacokinetics similar to those of moxifloxacin yet is more active than moxifloxacin during both the initial and continuation phases of treatment in a murine model. These results warrant further preclinical evaluation of DC-159a in selected drug combinations against drug-susceptible and fluoroquinolone-resistant tuberculosis.
Mupirocin Resistance in Staphylococcus aureus Causing Recurrent Skin and Soft Tissue Infections in Children
Authors: McNeil J. Chase , Hulten Kristina G. , Kaplan Sheldon L. , Mason Edward O. 
Published: February 2011

ABSTRACT

Staphylococcus aureus
resistance to mupirocin is often caused by acquisition of a novel isoleucyl-tRNA synthetase encoded on the plasmid gene
mupA
. We tested
S. aureus
isolates from children at Texas Children's Hospital with recurrent skin and soft tissue infections for mupirocin resistance and
mupA
. Of 136 isolates, 20 were resistant to mupirocin (14.7%). Fifteen isolates (11%) carried
mupA
, and the gene was more common in methicillin-susceptible
S. aureus
(21.4%) than methicillin-resistant
S. aureus
(8.3%;
P
= 0.03). Seven of 20 mupirocin-resistant isolates displayed clindamycin resistance.
Effect of Antibiotic Treatment on the Intestinal Metabolome
Authors: Antunes L. Caetano M. , Han Jun , Ferreira Rosana B. R. , Lolić Petra , Borchers Christoph H. , Finlay B. Brett 
Published: February 2011

ABSTRACT
The importance of the mammalian intestinal microbiota to human health has been intensely studied over the past few years. It is now clear that the interactions between human hosts and their associated microbial communities need to be characterized in molecular detail if we are to truly understand human physiology. Additionally, the study of such host-microbe interactions is likely to provide us with new strategies to manipulate these complex systems to maintain or restore homeostasis in order to prevent or cure pathological states. Here, we describe the use of high-throughput metabolomics to shed light on the interactions between the intestinal microbiota and the host. We show that antibiotic treatment disrupts intestinal homeostasis and has a profound impact on the intestinal metabolome, affecting the levels of over 87% of all metabolites detected. Many metabolic pathways that are critical for host physiology were affected, including bile acid, eicosanoid, and steroid hormone synthesis. Dissecting the molecular mechanisms involved in the impact of beneficial microbes on some of these pathways will be instrumental in understanding the interplay between the host and its complex resident microbiota and may aid in the design of new therapeutic strategies that target these interactions.
Frequency of Voriconazole Resistance
In Vitro
among Spanish Clinical Isolates of
Candida
spp. According to Breakpoints Established by the Antifungal Subcommittee of the European Committee on Antimicrobial Susceptibility Testing
Authors: Cuenca-Estrella M. , Gomez-Lopez A. , Cuesta I. , Zaragoza O. , Mellado E. , Rodriguez-Tudela J. L. 
Published: February 2011

ABSTRACT

A total of 4,226 Spanish clinical isolates of
Candida
spp. were analyzed to assess resistance to voriconazole according to breakpoints established by the European Committee for Antimicrobial Susceptibility Testing (where susceptibility [S] to voriconazole corresponds to a MIC of ≤0.12 mg/liter). Resistance was uncommon among
Candida albicans
(5%),
C. parapsilosis
(1.2%), and
C. tropicalis
(11%) isolates. Voriconazole MICs of >0.12 mg/liter were more frequent among
Candida glabrata
and
C. krusei
isolates. A significant percentage of voriconazole-resistant strains came from oropharyngeal infections and exhibited high MICs of other azoles.