scholarly journals In VitroActivity of Solithromycin against Erythromycin-Resistant Streptococcus agalactiae

2013 ◽  
Vol 58 (3) ◽  
pp. 1693-1698 ◽  
Author(s):  
Giorgio Piccinelli ◽  
Prabhavathi Fernandes ◽  
Carlo Bonfanti ◽  
Francesca Caccuri ◽  
Arnaldo Caruso ◽  
...  
Keyword(s):  
Streptococcus Agalactiae ◽  
Group B Streptococcus ◽  
Phenotypic Characterization ◽  
Content Type ◽  
Resistant Strains ◽  
Group B ◽  
Microdilution Broth

ABSTRACTThein vitroantibacterial activity of solithromycin (CEM-101) against macrolide-resistant isolates (n= 62) ofStreptococcus agalactiae(group B streptococcus [GBS]) was determined. Phenotypic characterization of macrolide-resistant strains was performed by double-disc diffusion testing. A multiplex PCR was used to identify theerm(B),erm(TR), andmef(A/E) genes, capsular genotypes, and alpha-like (Alp) protein genes from the GBS strains. Determination of MIC was carried out using the microdilution broth method. The Etest method was used for penicillin, azithromycin, clarithromycin, and erythromycin. Solithromycin had a MIC50of ≤0.008 μg/ml and a MIC90of 0.015 μg/ml against macrolide-susceptibleS. agalactiae. These MICs were lower than those displayed by penicillin (MIC50of 0.032 μg/ml and MIC90of 0.047 μg/ml), the antibiotic agent of choice for prophylaxis and treatment of GBS infections. Against macrolide-resistantS. agalactiae, solithromycin had a MIC50of 0.03 μg/ml and a MIC90of 0.125 μg/ml. Againsterm(B) strains, solithromycin had a MIC50of 0.03 μg/ml and a MIC90of 0.06 μg/ml, while againstmef(A) strains, it had a MIC50of 0.03 μg/ml and a MIC90of 0.125 μg/ml. Most erythromycin-resistant GBS strains were of serotype V (64.5%) and associated significantly withalp2-3. Moreover, a statistically significant association was observed between the constitutive macrolide-lincosamide-streptogramin B resistance (cMLSB) phenotype and theerm(B) gene-carrying strains, thealp2-3gene and the M phenotype, and themef(A/E) gene andepsilon. Overall, our results show that solithromycin had lower or similar MICs than penicillin and potent activity against macrolide-resistant strains independent of their genotype or phenotype, representing a valid therapeutic alternative where β-lactams cannot be used.

scholarly journals Cellular Management of Zinc in Group B Streptococcus Supports Bacterial Resistance against Metal Intoxication and Promotes Disseminated Infection

mSphere ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Matthew J. Sullivan ◽  
Kelvin G. K. Goh ◽  
Glen C. Ulett
Keyword(s):  
Streptococcus Agalactiae ◽  
Bacterial Resistance ◽  
Group B Streptococcus ◽  
Systemic Infection ◽  
Metal Stress ◽  
Mechanisms Of Resistance ◽  
Content Type ◽  
Group B ◽  
Zn Stress

ABSTRACT Zinc is an essential trace element for normal bacterial physiology but, divergently, can intoxicate bacteria at high concentrations. Here, we define the molecular systems for Zn detoxification in Streptococcus agalactiae, also known as group B streptococcus, and examine the effects of resistance to Zn stress on virulence. We compared the growth of wild-type bacteria and mutants deleted for the Zn exporter, czcD, and the response regulator, sczA, using Zn-stress conditions in vitro. Macrophage antibiotic protection assays and a mouse model of disseminated infection were used to assess virulence. Global bacterial transcriptional responses to Zn stress were defined by RNA sequencing and quantitative reverse transcription-PCR. czcD and sczA enabled S. agalactiae to survive Zn stress, with the putative CzcD efflux system activated by SczA. Additional genes activated in response to Zn stress encompassed divalent cation transporters that contribute to regulation of Mn and Fe homeostasis. In vivo, the czcD-sczA Zn management axis supported virulence in the blood, heart, liver, and bladder. Additionally, several genes not previously linked to Zn stress in any bacterium, including, most notably, arcA for arginine deamination, also mediated resistance to Zn stress, representing a novel molecular mechanism of bacterial resistance to metal intoxication. Taken together, these findings show that S. agalactiae responds to Zn stress by sczA regulation of czcD, with additional novel mechanisms of resistance supported by arcA, encoding arginine deaminase. Cellular management of Zn stress in S. agalactiae supports virulence by facilitating bacterial survival in the host during systemic infection. IMPORTANCE Streptococcus agalactiae, also known as group B streptococcus, is an opportunistic pathogen that causes various diseases in humans and animals. This bacterium has genetic systems that enable zinc detoxification in environments of metal stress, but these systems remain largely undefined. Using a combination of genomic, genetic, and cellular assays, we show that this pathogen controls Zn export through CzcD to manage Zn stress and utilizes a system of arginine deamination never previously linked to metal stress responses in bacteria to survive metal intoxication. We show that these systems are crucial for survival of S. agalactiae in vitro during Zn stress and also enhance virulence during systemic infection in mice. These discoveries establish new molecular mechanisms of resistance to metal intoxication in bacteria; we suggest these mechanisms operate in other bacteria as a way to sustain microbial survival under conditions of metal stress, including in host environments.

scholarly journals Substrate Proteins Take Shape at an Improved Bacterial Translocon

2018 ◽  
Vol 201 (1) ◽  
Author(s):  
Donald Oliver
Keyword(s):  
Protein Transport ◽  
Protein Translocation ◽  
Membrane Vesicles ◽  
Transport Models ◽  
Content Type ◽  
Rate Limiting ◽  
Substrate Proteins

ABSTRACTCharacterization of Sec-dependent bacterial protein transport has often relied on anin vitroprotein translocation system comprised in part ofEscherichia coliinverted inner membrane vesicles or, more recently, purified SecYEG translocons reconstituted into liposomes using mostly a single substrate (proOmpA). A paper published in this issue (P. Bariya and L. Randall, J Bacteriol 201:e00493-18, 2019, https://doi.org/10.1128/JB.00493-18) finds that inclusion of SecA protein during SecYEG proteoliposome reconstitution dramatically improves the number of active translocons. This experimentally useful and intriguing result that may arise from SecA membrane integration properties is discussed here. Furthermore, determination of the rate-limiting transport step for nine different substrates implicates the mature region distal to the signal peptide in the observed rate constant differences, indicating that more nuanced transport models that respond to differences in protein sequence and structure are needed.

scholarly journals Chromosomally and Extrachromosomally Mediated High-Level Gentamicin Resistance in Streptococcus agalactiae

2016 ◽  
Vol 60 (3) ◽  
pp. 1702-1707 ◽  
Author(s):  
Parham Sendi ◽  
Martina Furitsch ◽  
Stefanie Mauerer ◽  
Carlos Florindo ◽  
Barbara C. Kahl ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Streptococcus Agalactiae ◽  
Molecular Mechanisms ◽  
The Other ◽  
Content Type ◽  
Gentamicin Resistance ◽  
Group B ◽  
High Level ◽  
Plasmid Purification

Streptococcus agalactiae(group BStreptococcus[GBS]) is a leading cause of sepsis in neonates. The rate of invasive GBS disease in nonpregnant adults also continues to climb. Aminoglycosides alone have little or no effect on GBS, but synergistic killing with penicillin has been shownin vitro. High-level gentamicin resistance (HLGR) in GBS isolates, however, leads to the loss of a synergistic effect. We therefore performed a multicenter study to determine the frequency of HLGR GBS isolates and to elucidate the molecular mechanisms leading to gentamicin resistance. From eight centers in four countries, 1,128 invasive and colonizing GBS isolates were pooled and investigated for the presence of HLGR. We identified two strains that displayed HLGR (BSU1203 and BSU452), both of which carried theaacA-aphDgene, typically conferring HLGR. However, only one strain (BSU1203) also carried the previously described chromosomal gentamicin resistance transposon designated Tn3706. For the other strain (BSU452), plasmid purification and subsequent DNA sequencing resulted in the detection of plasmid pIP501 carrying a remnant of a Tn3family transposon. Its ability to confer HLGR was proven by transfer into anEnterococcus faecalisisolate. Conversely, loss of HLGR was documented after curing both GBS BSU452 and the transformedE. faecalisstrain from the plasmid. This is the first report showing plasmid-mediated HLGR in GBS. Thus, in our clinical GBS isolates, HLGR is mediated both chromosomally and extrachromosomally.

scholarly journals In Vitro Isolation and Characterization of Oxazolidinone-Resistant Mycobacterium tuberculosis

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Matthew B. McNeil ◽  
Devon D. Dennison ◽  
Catherine D. Shelton ◽  
Tanya Parish
Keyword(s):  
Mycobacterium Tuberculosis ◽  
23S Rrna ◽  
Clinical Settings ◽  
Content Type ◽  
Isolation And Characterization ◽  
Mutant Strains ◽  
Ribosomal Protein L3 ◽  
Resistant Strains

ABSTRACT Oxazolidinones are promising candidates for the treatment of Mycobacterium tuberculosis infections. We isolated linezolid-resistant strains from H37Rv (Euro-American) and HN878 (East-Asian) strains; resistance frequencies were similar in the two strains. Mutations were identified in ribosomal protein L3 (RplC) and the 23S rRNA (rrl). All mutant strains were cross resistant to sutezolid; a subset was cross resistant to chloramphenicol. Mutations in rrl led to growth impairment and decreased fitness that may limit spread in clinical settings.

scholarly journals Molecular and phenotypic characterization of invasive group B streptococcus strains from infants in Norway 2006–2007

2009 ◽  
Vol 15 (12) ◽  
pp. 1182-1185 ◽  
Author(s):  
H. Bergseng ◽  
J.E. Afset ◽  
A. Radtke ◽  
K. Loeseth ◽  
R.V. Lyng ◽  
...  
Keyword(s):  
Group B Streptococcus ◽  
Phenotypic Characterization ◽  
Invasive Group ◽  
Group B

scholarly journals Epidemiological Characterization of Group B Streptococcus Infections in Alberta, Canada: An Update from 2014 to 2020

2021 ◽  
Author(s):  
Angela Ma ◽  
L. Alexa Thompson ◽  
Thomas Corsiatto ◽  
Donna Hurteau ◽  
Gregory J. Tyrrell
Keyword(s):  
Early Onset ◽  
Late Onset ◽  
Group B Streptococcus ◽  
Content Type ◽  
Adult Disease ◽  
Invasive Infections ◽  
Group B ◽  
Epidemiological Characterization

This work describes the epidemiology of invasive infections caused by the bacterium group B Streptococcus (GBS) in Alberta, Canada. We show that rates of invasive GBS disease have increased from 2014 to 2020 for both adult disease and late-onset disease in neonates, whereas the rate of early onset disease in neonates has decreased. We also show that the rate of resistance to erythromycin (an antibiotic used to treat GBS) has also increased in this time.

scholarly journals Whole-Genome Shotgun Sequence of Streptococcus agalactiae Sequence Type 176 Strain 3966RFQB from a Dairy Herd in Selangor, Malaysia

2019 ◽  
Vol 8 (6) ◽  
Author(s):  
A. Bashir ◽  
Z. Zunita ◽  
F. F. A. Jesse ◽  
S. Z. Ramanoon ◽  
M. L. Mohd-Azmi
Keyword(s):  
Streptococcus Agalactiae ◽  
Group B Streptococcus ◽  
Bovine Mastitis ◽  
Dairy Herd ◽  
Sequence Type ◽  
Control Measures ◽  
Content Type ◽  
Whole Genome Shotgun Sequence ◽  
Genome Shotgun Sequence ◽  
Group B

Streptococcus agalactiae, commonly known as group B streptococcus (GBS), is among the most implicated pathogens in bovine mastitis worldwide. Proper control measures can curb both economic and public health effects it may cause.

scholarly journals Characterization of Clinical and Carrier Streptococcus agalactiae and Prophage Contribution to the Strain Variability

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1323
Author(s):  
Aneta Lichvariková ◽  
Katarina Soltys ◽  
Tomas Szemes ◽  
Livia Slobodnikova ◽  
Gabriela Bukovska ◽  
...  
Keyword(s):  
Streptococcus Agalactiae ◽  
Bacterial Infections ◽  
Group B Streptococcus ◽  
Host Bacterium ◽  
Phage Integrase ◽  
Integration Sites ◽  
Group A ◽  
Pcr Method ◽  
Group B

Streptococcus agalactiae (group B Streptococcus, GBS) represents a leading cause of invasive bacterial infections in newborns and is also responsible for diseases in older and immunocompromised adults. Prophages represent an important factor contributing to the genome plasticity and evolution of new strains. In the present study, prophage content was analyzed in human GBS isolates. Thirty-seven prophages were identified in genomes of 20 representative sequenced strains. On the basis of the sequence comparison, we divided the prophages into eight groups named A–H. This division also corresponded to the clustering of phage integrase, even though several different integration sites were observed in some relative prophages. Next, PCR method was used for detection of the prophages in 123 GBS strains from adult hospitalized patients and from pregnancy screening. At least one prophage was present in 105 isolates (85%). The highest prevalence was observed for prophage group A (71%) and satellite prophage group B (62%). Other groups were detected infrequently (1–6%). Prophage distribution did not differ between clinical and screening strains, but it was unevenly distributed in MLST (multi locus sequence typing) sequence types. High content of full-length and satellite prophages detected in present study implies that prophages could be beneficial for the host bacterium and could contribute to evolution of more adapted strains.

scholarly journals Identification of Major Outer Surface Proteins of Streptococcus agalactiae

2002 ◽  
Vol 70 (3) ◽  
pp. 1254-1259 ◽  
Author(s):  
Martin J. G. Hughes ◽  
Joanne C. Moore ◽  
Jonathan D. Lane ◽  
Rebecca Wilson ◽  
Philippa K. Pribul ◽  
...  
Keyword(s):  
Outer Surface ◽  
Streptococcus Agalactiae ◽  
Expression System ◽  
Group B Streptococcus ◽  
Phosphoglycerate Kinase ◽  
Peptide Sequencing ◽  
Surface Proteins ◽  
Outer Surface Proteins ◽  
Group B

ABSTRACT To identify the major outer surface proteins of Streptococcus agalactiae (group B streptococcus), a proteomic analysis was undertaken. An extract of the outer surface proteins was separated by two-dimensional electrophoresis. The visualized spots were identified through a combination of peptide sequencing and reverse genetic methodologies. Of the 30 major spots identified as S. agalactiae specific, 27 have been identified. Six of these proteins, previously unidentified in S. agalactiae, were sequenced and cloned. These were ornithine carbamoyltransferase, phosphoglycerate kinase, nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase, purine nucleoside phosphorylase, enolase, and glucose-6-phosphate isomerase. Using a gram-positive expression system, we have overexpressed two of these proteins in an in vitro system. These recombinant, purified proteins were used to raise antisera. The identification of these proteins as residing on the outer surface was confirmed by the ability of the antisera to react against whole, live bacteria. Further, in a neonatal-animal model system, we demonstrate that some of these sera are protective against lethal doses of bacteria. These studies demonstrate the successful application of proteomics as a technique for identifying vaccine candidates.

scholarly journals NAD+ pool depletion as a signal for the Rex regulon involved in Streptococcus agalactiae virulence

2021 ◽  
Vol 17 (8) ◽  
pp. e1009791
Author(s):  
Thierry Franza ◽  
Annika Rogstam ◽  
Saravanamuthu Thiyagarajan ◽  
Matthew J. Sullivan ◽  
Aurelie Derré-Bobillot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Streptococcus Agalactiae ◽  
Group B Streptococcus ◽  
Virulence Gene ◽  
Opportunistic Pathogen ◽  
Virulence Gene Expression ◽  
Gram Positive Bacteria ◽  
Virulence Factor Gene ◽  
Group B

In many Gram-positive bacteria, the redox-sensing transcriptional repressor Rex controls central carbon and energy metabolism by sensing the intra cellular balance between the reduced and oxidized forms of nicotinamide adenine dinucleotide; the NADH/NAD+ ratio. Here, we report high-resolution crystal structures and characterization of a Rex ortholog (Gbs1167) in the opportunistic pathogen, Streptococcus agalactiae, also known as group B streptococcus (GBS). We present structures of Rex bound to NAD+ and to a DNA operator which are the first structures of a Rex-family member from a pathogenic bacterium. The structures reveal the molecular basis of DNA binding and the conformation alterations between the free NAD+ complex and DNA-bound form of Rex. Transcriptomic analysis revealed that GBS Rex controls not only central metabolism, but also expression of the monocistronic rex gene as well as virulence gene expression. Rex enhances GBS virulence after disseminated infection in mice. Mechanistically, NAD+ stabilizes Rex as a repressor in the absence of NADH. However, GBS Rex is unique compared to Rex regulators previously characterized because of its sensing mechanism: we show that it primarily responds to NAD+ levels (or growth rate) rather than to the NADH/NAD+ ratio. These results indicate that Rex plays a key role in GBS pathogenicity by modulating virulence factor gene expression and carbon metabolism to harvest nutrients from the host.

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