scholarly journals Revising the Role of the Pneumococcal vex-vncRS Locus in Vancomycin Tolerance

2004 ◽  
Vol 186 (24) ◽  
pp. 8463-8471 ◽  
Author(s):  
Wolfgang Haas ◽  
Jack Sublett ◽  
Deepak Kaushal ◽  
Elaine I. Tuomanen
Keyword(s):  
Abc Transporter ◽  
Multidrug Resistant ◽  
Loss Of Function ◽  
Two Component System ◽  
Exact Function ◽  
Invasive Infections ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Vancomycin Treatment

ABSTRACT Vancomycin is used increasingly to treat invasive infections caused by multidrug-resistant Streptococcus pneumoniae. Although no vancomycin-resistant strains have been isolated to date, tolerant strains that fail to die rapidly and that cause relapsing disease have been described. The vex123-pep27 -vncRS locus, consisting of an ABC transporter, a presumed signaling peptide, and a two-component system, respectively, has been implicated in vancomycin tolerance. Recent findings, however, challenged this model. The data presented here indicate that erythromycin in the growth medium induces a vancomycin-tolerant phenotype and that loss of function of Pep27 or VncRS does not alter autolysis. However, a role for the ABC transporter encoded by the vex123 genes in tolerance was confirmed. A vex3 mutant was considerably more tolerant to vancomycin treatment than the wild-type strain T4, and the strength of the phenotype depended on the orientation of the resistance cassette used to construct the mutant. Microarray results suggested a number of genes that might be involved in tolerance in the vex3 mutant. Although the exact function and regulation of the vex123-pep27 -vncRS locus remains to be determined, several factors influence the autolysis behavior of S. pneumoniae, including the bacterial capsule, erythromycin, and the lytA and vex3 gene products.

scholarly journals Staphylococcus aureus Infections in Malaysia: A Review of Antimicrobial Resistance and Characteristics of the Clinical Isolates, 1990–2017

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 128 ◽  
Author(s):  
Ainal Mardziah Che Hamzah ◽  
Chew Chieng Yeo ◽  
Suat Moi Puah ◽  
Kek Heng Chua ◽  
Ching Hoong Chew
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Sccmec Type ◽  
Epidemiological Data ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Type Iv ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Comprehensive Surveillance

Staphylococcus aureus is an important nosocomial pathogen and its multidrug resistant strains, particularly methicillin-resistant S. aureus (MRSA), poses a serious threat to public health due to its limited therapeutic options. The increasing MRSA resistance towards vancomycin, which is the current drug of last resort, gives a great challenge to the treatment and management of MRSA infections. While vancomycin resistance among Malaysian MRSA isolates has yet to be documented, a case of vancomycin resistant S. aureus has been reported in our neighboring country, Indonesia. In this review, we present the antimicrobial resistance profiles of S. aureus clinical isolates in Malaysia with data obtained from the Malaysian National Surveillance on Antimicrobial Resistance (NSAR) reports as well as various peer-reviewed published records spanning a period of nearly three decades (1990–2017). We also review the clonal types and characteristics of Malaysian S. aureus isolates, where hospital-associated (HA) MRSA isolates tend to carry staphylococcal cassette chromosome mec (SCCmec) type III and were of sequence type (ST)239, whereas community-associated (CA) isolates are mostly SCCmec type IV/V and ST30. More comprehensive surveillance data that include molecular epidemiological data would enable further in-depth understanding of Malaysian S. aureus isolates.

scholarly journals The Biology and Role of Interleukin-32 in Tuberculosis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wu Li ◽  
Wanyan Deng ◽  
Jianping Xie
Keyword(s):  
Multidrug Resistant ◽  
Drug Resistant ◽  
Host Molecule ◽  
Tuberculosis Control ◽  
Promising Alternative ◽  
Extensively Drug Resistant ◽  
Important Host ◽  
Resistant Strains ◽  
Drug Resistant Strains

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of morbidity and mortality globally, with nearly 10.4 million new cases of incidence and over 1.7 million deaths annually. Drug-resistant M. tuberculosis strains, especially multidrug-resistant or extensively drug-resistant strains, have further intensified the problem associated with tuberculosis control. Host-directed therapy is a promising alternative for tuberculosis control. IL-32 is increasingly recognized as an important host molecule against tuberculosis. In this review, we highlight the proinflammatory properties of IL-32 and the mode of action of IL-32 in mycobacterial infections to inspire the development of novel immunity-based countermeasures and host-directed therapies against tuberculosis.

scholarly journals An Early Response to Environmental Stress Involves Regulation of OmpX and OmpF, Two Enterobacterial Outer Membrane Pore-Forming Proteins

2007 ◽  
Vol 51 (9) ◽  
pp. 3190-3198 ◽  
Author(s):  
Myrielle Dupont ◽  
Chloë E. James ◽  
Jacqueline Chevalier ◽  
Jean-Marie Pagès
Keyword(s):  
Outer Membrane ◽  
Early Response ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Membrane Pore ◽  
Bacterial Response ◽  
External Stresses ◽  
Resistant Strains ◽  
Pore Forming Proteins

ABSTRACT Bacterial adaptation to external stresses and toxic compounds is a key step in the emergence of multidrug-resistant strains that are a serious threat to human health. Although some of the proteins and regulators involved in antibiotic resistance mechanisms have been described, no information is available to date concerning the early bacterial response to external stresses. Here we report that the expression of ompX, encoding an outer membrane protein, is increased during early exposure to drugs or environmental stresses. At the same time, the level of ompF porin expression is noticeably affected. Because of the role of these proteins in membrane permeability, these data suggest that OmpF and OmpX are involved in the control of the penetration of antibiotics such as β-lactams and fluoroquinolones through the enterobacterial outer membrane. Consequently, the early control of ompX and ompF induced by external stresses may represent a preliminary response to antibiotics, thus triggering the initial bacterial line of defense against antibiotherapy.

scholarly journals Is there any association between antibiotic resistance and virulence genes in Enterococcus isolates?

2019 ◽  
Vol 6 (12) ◽  
pp. 310-315
Author(s):  
Nergis Aşgın ◽  
Emre Taşkın
Keyword(s):  
Antibiotic Resistance ◽  
Virulence Genes ◽  
Multidrug Resistant ◽  
Automated System ◽  
High Frequencies ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
High Level

Objective: In this study, we aim to determine the frequency of antibiotic resistance and five virulence genes in Enterococcus species and the relationship between antibiotic resistance and virulence genes. Material and Methods: A total of 86 Enterococcus strains isolated from inpatients between 2015 and 2016 were included. Identification and antibiotic susceptibilities of strains were determined using a BD Phoenix fully automated system. The presence of virulence-associated genes (esp, gel E, asa1, hyl, and cyl) were investigated by using PCR method. Results: Of the 86 Enterococcus strains, 53 (61.6%) and 33 (38.4%) were Enterococcus faecium and Enterococcus faecalis, respectively. Vancomycin and high-level gentamicin resistance (HLGR) in E. faecalis strains were 0.6% and 60.6%, respectively. Furthermore, 52 of the 53 E. faecium strains were both vancomycin-resistant and HLGR. The frequency of esp, gel E, asa1, cyl, and hyl was 91.9%, 60.5%, 54.7%, 43%, and 26.7%, respectively.  The asa 1, cyl, and gel E genes were detected at high frequencies in vancomycin-susceptible and non-HLGR strains, whereas hyl gene was detected at high frequencies in vancomycin-resistant and HLGR strains. Conclusion: Virulence genes were more frequent in vancomycin-susceptible and non-HLGR Enterococcus strains than in the resistant strains. Although infections caused by multidrug-resistant strains are difficult to treat, it should be considered that susceptible strains have more virulence genes. This may reduce the in vivo efficacy of drugs and lead to treatment failures. Therefore, in addition to the in vitro susceptibilities of drugs, clinical efficacy should be monitored.

Antimicrobial-Resistant Gram-Positive Bacteria in PD Peritonitis and the Newer Antibiotics Used to Treat Them

2005 ◽  
Vol 25 (4) ◽  
pp. 313-319 ◽  
Author(s):  
William Salzer
Keyword(s):  
Methicillin Resistant Staphylococcus Aureus ◽  
Natural Habitat ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
The Past ◽  
Vancomycin Resistant Enterococci ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Novel Antibiotics

The incidence of resistant gram-positive bacteria in nosocomial and, more recently, community-acquired infections is increasing. Staphylococci, because of their natural habitat on the skin, have always been the leading cause of peritonitis in patients receiving peritoneal dialysis (PD). These organisms have demonstrated a remarkable ability to develop resistance to antibiotics, first with penicillin, then antistaphylococcal penicillins (methicillin-resistant Staphylococcus aureus), and more recently, strains expressing resistance to vancomycin (vancomycin-intermediate and vancomycin-resistant S. aureus) have emerged. Enterococci are normal inhabitants of the gastrointestinal tract and occasionally cause PD peritonitis. In the past 15 years, vancomycin-resistant enterococci have emerged as significant pathogens in many areas. In the past 5 years, novel antibiotics that have activity on gram-positive bacteria, including vancomycin-resistant strains, have become available. The problem of resistant gram-positive bacteria in PD peritonitis, their therapy, and the role of these newer agents, quinupristin/dalfopristin, linezolid, and daptomycin, are reviewed.

In vitro evaluation of a novel ketolide antimicrobial agent, RU-64004.

1997 ◽  
Vol 41 (2) ◽  
pp. 454-459 ◽  
Author(s):  
C Jamjian ◽  
D J Biedenbach ◽  
R N Jones
Keyword(s):  
Moraxella Catarrhalis ◽  
In Vitro Tests ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Beta Hemolytic Streptococcus ◽  
Serious Infections ◽  
Resistant Strains ◽  
Vancomycin Resistant

Ketolides, a novel macrolide subclass, possess a mode of action that is similar to that of structurally related macrolide-lincosamide-streptogramin (MLS) compounds. By using reference in vitro tests, the in vitro activity of RU-64004 was compared to those of six other MLS compounds against more than 800 clinical pathogens, including 356 gram-positive organisms. The spectrum of activity of the ketolide was most similar to that of clindamycin versus staphylococci and streptococci and superior to those of all macrolides tested against oxacillin-resistant staphylococci and vancomycin-resistant (vanA, vanB, and vanC) enterococcal isolates. The activity of the ketolide was greater than those of the macrolides, azalides, or clindamycin tested against vancomycin-susceptible enterococci (MICs at which 90% of isolates are inhibited [MIC90S], 0.25 to 4 micrograms/ml), penicillin-resistant pneumococci (MIC90, 0.25 micrograms/ml), and most beta-hemolytic streptococci. All Streptococcus pneumoniae and beta-hemolytic streptococcus strain were inhibited by ketolide concentrations of < or = 0.25 micrograms/ml. Against 165 erythromycin-resistant strains, RU-64004 inhibited (MICs, < or = 0.5 micrograms/ml) approximately one-third of staphylococci, all streptococci, and slightly more than one-half of the enterococci. Quinupristin-dalfopristin (a streptogramin combination) was active against all tested isolates with the exception of non-Enterococcus faecium enterococci, against which the ketolide exhibited greater potency (MIC50S, 0.03 to 2 micrograms/ml). The ketolide was also active against Haemophilus influenzae (MIC90, 2 micrograms/ml), Moraxella catarrhalis (MIC90, 0.12 micrograms/ml), pathogenic Neisseria spp. (MIC90, 0.5 micrograms/ml), and many gram-positive anaerobes (MIC90, 0.5 micrograms/ml). RU-64004 may enhance the role of macrolide drugs in the treatment of some serious infections caused by MLS-resistant gram-positive organisms.

The Epidemiology of Multidrug-ResistantAcinetobacter BaumanniiDoes the Community Represent a Reservoir?

2003 ◽  
Vol 24 (4) ◽  
pp. 275-279 ◽  
Author(s):  
Cosmina Zeana ◽  
Elaine Larson ◽  
Jyoti Sahni ◽  
S. J. Bayuga ◽  
Fann Wu ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Molecular Typing ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Community Members ◽  
Community Residents ◽  
Potential Reservoir ◽  
Resistance Patterns ◽  
Resistant Strains

AbstractObjective:To explore the role of the community as a potential reservoir forAcinetobacter baumannii.Design:Antimicrobial resistance patterns and genotypes ofA. baumanniiisolates from patients in two Manhattan hospitals were compared with those ofA. baumanniiisolates from the hands of community members.Results:A total of 103 isolates from two hospitals (hospital A, 81; hospital B, 22) and 23 isolates from community residents were studied. Of the hospital isolates, 36.6% were multidrug resistant (hospital A, 68.2%; hospital B, 27.8%). In contrast, there were no multidrug-resistant isolates from the community (P< .005 between hospital and community). The prevalence ofA. baumanniion the hands of community residents was 10.4% (23 of 222). By molecular typing, 42 strains of A.baumanniiwere identified. Of the isolates from hospital A and hospital B, 55.6% (45 of 81) and 68.2% (15 of 22), respectively, were indistinguishable or closely related. In contrast, most community (83.3%) isolates were unrelated (P= .001 between hospital and community).Conclusion:Acinetobacterisolates from the community, characterized by a large variety of unrelated strains (83.3%), were distinct from the hospital isolates, of which 58.3% were closely related. The absence of multidrug-resistant strains in the community compared with 36.6% prevalence among hospital isolates suggests that the reservoir for epidemic strains resides in the hospital environment itself. To our knowledge, this is the first study to examine the community as a potential reservoir for hospital strains ofA. baumannii.

scholarly journals Non-pncAGene-Mutated but Pyrazinamide-Resistant Mycobacterium tuberculosis: Why Is That?

2017 ◽  
Vol 55 (6) ◽  
pp. 1920-1927 ◽  
Author(s):  
Jim Werngren ◽  
Erik Alm ◽  
Mikael Mansjö
Keyword(s):  
Susceptibility Testing ◽  
Gene Mutations ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Molecular Techniques ◽  
Content Type ◽  
Resistant Strains ◽  
Clear Majority

ABSTRACTPyrazinamide (PZA) is a key component for the effective treatment of drug-susceptible and PZA-susceptible multidrug-resistant (MDRPZA-S) tuberculosis (TB).pncAgene mutations are usually detected in a clear majority (>90%) of PZA-resistant strains but obviously not in all. Rapid and reliable PZA drug susceptibility testing (DST) is critical whenever PZA is to be used in a treatment regimen, not least for the treatment of MDRPZA-STB. In this study, we selected 26 PZA-resistant isolates reported to carry a wild-typepncAgene. To confirm resistance, susceptibility testing was repeated using 100 mg/liter and 200 mg/liter PZA for all the 26 isolates and Sanger sequencing was repeated on the 18 isolates that remained PZA resistant. Apart from the eight isolates initially misclassified as PZA resistant, the retests identified three factors responsible for the phenotype-genotype discrepancy:panDorrpsAmutations identified by whole-genome sequencing (WGS) (n= 7), heteroresistance (n= 8), and mixed populations withMycobacterium avium(n= 3). Additionally, we performed WGS on 400 PZA-susceptible isolates and 15 consecutive MDRPZA-Rclinical isolates. Of the 400 PZA-susceptible isolates, only 1 harbored a nonsynonymouspncAmutation (Thr87Met), whereas a nonsynonymousrpsAmutation was found in 17 isolates. None of these isolates carried a nonsynonymouspanDmutation, while all 15 of the MDRPZA-Risolates harbored a nonsynonymouspncAmutation. Our findings indicate that it is necessary to consider the occurrence ofpanDmutations in PZA-resistant isolates, as well as heteroresistance, for the development and evaluation of new molecular techniques to ensure high-quality DST performance. The identification of nonsynonymousrpsAmutations in both PZA-susceptible and PZA-resistant isolates also implies that further studies are needed in order to determine the role ofrpsAin PZA resistance.

scholarly journals Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya

2021 ◽  
Author(s):  
Samuel Kariuki ◽  
Zoe A Dyson ◽  
Cecilia Mbae ◽  
Ronald Ngetich ◽  
Susan M Kavai ◽  
...  
Keyword(s):  
Informal Settlement ◽  
Acute Infection ◽  
Multidrug Resistant ◽  
Stool Culture ◽  
High Rate ◽  
Multiple Introductions ◽  
Resistant Strains ◽  
And Control ◽  
Control Study

AbstractUnderstanding the dynamics of infection and carriage of typhoid in endemic settings is critical to finding solutions to prevention and control. In a 3 year case-control study, we investigated typhoid among children aged <16 years (4,670 febrile cases and 8,549 age matched controls) living in an informal settlement, Nairobi, Kenya. 148 S. Typhi isolates from cases and 95 from controls (stool culture) were identified; a carriage frequency of 1%. Whole-genome sequencing showed 97% of cases and 88% of controls were genotype 4.3.1 (Haplotype58), with the majority of each (76% and 88%) being multidrug-resistant strains in 3 sublineages of H58 genotype (East Africa 1 (EA1), EA2, and EA3), with sequences from cases and carriers intermingled. The high rate of multidrug-resistant H58 S. Typhi, and the close phylogenetic relationships between carriers and controls, provides evidence for the role of carriers as a reservoir for the community spread of typhoid in this setting.

scholarly journals Helicobacter pylori antibiotic resistance and [13C]urea breath test values

2010 ◽  
Vol 59 (5) ◽  
pp. 588-591 ◽  
Author(s):  
Vincenzo De Francesco ◽  
Angelo Zullo ◽  
Federico Perna ◽  
Floriana Giorgio ◽  
Cesare Hassan ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Breath Test ◽  
Multidrug Resistant ◽  
Urea Breath Test ◽  
Predictive Role ◽  
Resistant Strains ◽  
13C Urea Breath Test ◽  
H Pylori

A correlation between δ over baseline (DOB) values of the [13C]urea breath test (UBT) and Helicobacter pylori clarithromycin resistance has been reported, suggesting a possible predictive role of UBT in therapeutic outcome. However, available data are limited and conflicting. This study aimed to clarify this issue, assessing the possible relationship between H. pylori resistance towards different antibiotics (clarithromycin, metronidazole and levofloxacin) and UBT values. The data showed similar DOB values between susceptible and resistant strains for clarithromycin (46.9±32.3 vs 45.7±30.6; P=0.8), metronidazole (46.4±29.6 vs 47.4±37.9; P=0.8), and levofloxacin (45.0±30.2 vs 54.2±38.4; P=0.08). Likewise, comparable DOB values were observed between susceptible and multidrug-resistant strains (45.4±29.6 vs 54.8±44.8; P=0.1). In conclusion, our data failed to find a significant correlation between UBT values and H. pylori antibiotic resistance.

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