scholarly journals Targeting of muralytic enzymes to the cell division site of Gram-positive bacteria: repeat domains direct autolysin to the equatorial surface ring of Staphylococcus aureus

1998 ◽  
Vol 17 (16) ◽  
pp. 4639-4646 ◽  
Author(s):  
T. Baba
mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Kristoffer T. Bæk ◽  
Lisa Bowman ◽  
Charlotte Millership ◽  
Mia Dupont Søgaard ◽  
Volkhard Kaever ◽  
...  

ABSTRACTLipoteichoic acid (LTA) is an important cell wall component of Gram-positive bacteria and a promising target for the development of vaccines and antimicrobial compounds againstStaphylococcus aureus. Here we demonstrate that mutations in the conditionally essentialltaS(LTA synthase) gene arise spontaneously in anS. aureusmutant lacking the ClpX chaperone. A wide variety ofltaSmutations were selected, and among these, a substantial portion resulted in premature stop codons and other changes predicted to abolish LtaS synthesis. Consistent with this assumption, theclpX ltaSdouble mutants did not produce LTA, and genetic analyses confirmed that LTA becomes nonessential in the absence of the ClpX chaperone. In fact, inactivation ofltaSalleviated the severe growth defect conferred by theclpXdeletion. Microscopic analyses showed that the absence of ClpX partly alleviates the septum placement defects of an LTA-depleted strain, while other phenotypes typical of LTA-negativeS. aureusmutants, including increased cell size and decreased autolytic activity, are retained. In conclusion, our results indicate that LTA has an essential role in septum placement that can be bypassed by inactivating the ClpX chaperone.IMPORTANCELipoteichoic acid is an essential component of theStaphylococcus aureuscell envelope and an attractive target for the development of vaccines and antimicrobials directed against antibiotic-resistant Gram-positive bacteria such as methicillin-resistantS. aureusand vancomycin-resistant enterococci. In this study, we showed that the lipoteichoic acid polymer is essential for growth ofS. aureusonly as long as the ClpX chaperone is present in the cell. Our results indicate that lipoteichoic acid and ClpX play opposite roles in a pathway that controls two key cell division processes inS. aureus, namely, septum formation and autolytic activity. The discovery of a novel functional connection in the genetic network that controls cell division inS. aureusmay expand the repertoire of possible strategies to identify compounds or compound combinations that kill antibiotic-resistantS. aureus.


2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.


2014 ◽  
Vol 8 (3) ◽  
pp. 40-45
Author(s):  
Zina Hashem Shehab ◽  
Huda Suhail Abid ◽  
Sumaya Fadhil Hamad ◽  
Sara Haitham

The study was conducted to evaluate the inhibitory activity of methanol extract of Gardenia jasminoides leaves compared with leaf crude extracts for some organic solvents namely Methanol, Ethanol, Petroleum ether, Asetone and Chloroform on growth of some pathogenic bacteria and yeast, which included four gram positive isolates Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes and Bacillus cereus and gram negative isolates Escherichia coli, Salmonella typhi, Proteus vulgaris and Pseudomonas aeruginosa and some yeasts Candida albicans and Saccharomyces boulardii, by using well diffusion method. The inhibitory activity of extracts in the tested bacterial strains and yeasts was varied according to the type of extracting solvents and are tested microorganisms. The methanol callus extract which grown on Murashige and Skoog (MS) media by using (Naphthalen acitic acid) NAA and (Benzyle adenine) BA as growth regulator highly effective as compared to the other extracts as for inhibition of three gram positive bacteria and three gram negative bacteria,which include Staphylococcus aureus and, Proteus vulgaris, followed by acetone and ethanolic extracts which include two gram positive bacteria and two gram negative bacteria. All extracts had highly effect in growth of Candida albicans while all crude extracts didn’t show any sensitivity against Saccharomyces boulardii, and when we’d done (High Performance Liquid Chromatography) HPLC test for detection of some active compound we found Quinic acid, Iridiods glycosides and Crocin which its rate in fresh callus was higher than fresh leaves.


2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Sara Ceballos ◽  
Choon Kim ◽  
Derong Ding ◽  
Shahriar Mobashery ◽  
Mayland Chang ◽  
...  

ABSTRACT The activities of four oxadiazoles were investigated with 210 methicillin-resistant Staphylococcus aureus (MRSA) strains. MIC50 and MIC90 values of 1 to 2 and 4 μg/ml, respectively, were observed. We also evaluated the activity of oxadiazole ND-421 against other staphylococci and enterococci and in the presence of oxacillin for selected MRSA strains. The MIC for ND-421 is lowered severalfold in combination with oxacillin, as they synergize. The MIC90 of ND-421 against vancomycin-resistant enterococci is ≤1 μg/ml.


2021 ◽  
Author(s):  
Xiang-Na Guan ◽  
Tao Zhang ◽  
Teng Yang ◽  
Ze Dong ◽  
Song Yang ◽  
...  

The housekeeping sortase A (SrtA), a membrane-associated cysteine transpeptidase, is responsible for anchoring surface proteins to the cell wall peptidoglycan in Gram-positive bacteria. This process is essential for the regulation...


2012 ◽  
Vol 7 (5) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Alexis Peña ◽  
Luis Rojas ◽  
Rosa Aparicio ◽  
Libia Alarcón ◽  
José Gregorio Baptista ◽  
...  

The essential oil of the leaves of Espeletia nana Cuatrec, obtained by hydrodistillation, was analyzed by GC-MS, which allowed the identification of 24 components, which made up 99.9% of the oil. The most abundant compounds were α-pinene (38.1%), β-pinene (17.2%), myrcene (15.0%), spathulenol (4.2%), bicyclogermacrene (4.0%), α-zingiberene (4.0%), and γhimachalene (3.7%). Antibacterial activity was tested against Gram-positive and Gram-negative bacteria using the agar disk diffusion method. Activity was observed only against Gram-positive bacteria. MIC values were determined for Staphylococcus aureus ATCC 25923(200 μg/mL) and Enterococcus faecalis ATCC 29212 (600 μg/mL).


2004 ◽  
Vol 72 (5) ◽  
pp. 2710-2722 ◽  
Author(s):  
David Comfort ◽  
Robert T. Clubb

ABSTRACT Surface proteins in gram-positive bacteria are frequently required for virulence, and many are attached to the cell wall by sortase enzymes. Bacteria frequently encode more than one sortase enzyme and an even larger number of potential sortase substrates that possess an LPXTG-type cell wall sorting signal. In order to elucidate the sorting pathways present in gram-positive bacteria, we performed a comparative analysis of 72 sequenced microbial genomes. We show that sortase enzymes can be partitioned into five distinct subfamilies based upon their primary sequences and that most of their substrates can be predicted by making a few conservative assumptions. Most bacteria encode sortases from two or more subfamilies, which are predicted to function nonredundantly in sorting proteins to the cell surface. Only ∼20% of sortase-related proteins are most closely related to the well-characterized Staphylococcus aureus SrtA protein, but nonetheless, these proteins are responsible for anchoring the majority of surface proteins in gram-positive bacteria. In contrast, most sortase-like proteins are predicted to play a more specialized role, with each anchoring far fewer proteins that contain unusual sequence motifs. The functional sortase-substrate linkage predictions are available online (http://www.doe-mbi.ucla.edu/Services/Sortase/ ) in a searchable database.


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