DNA microarray analysis of Staphylococcus aureus from Nigeria and South Africa.

Staphylococcus aureus is an important human pathogen with an arsenal of virulence factors and a propensity to acquire antibiotic resistance genes. The understanding of the global epidemiology of S. aureus through the use of various typing methods is important in the detection and tracking of novel and epidemic clones in countries and regions. However, detailed information on antibiotic resistance and virulence genes of S. aureus, and its population structure is still limited in Africa. In this study, S. aureus isolates collected in South Africa (n = 38) and Nigeria (n = 2) from 2001-2004 were characterized by spa typing and DNA microarray. The combination of these two methods classified the isolates into seven spa types and three clonal complexes (CCs) i.e. t064-CC8 (n = 17), t037-CC8 (n = 8), t1257-CC8 (n = 6), t045-CC5 (n = 5), t951-CC8 (n = 1), t2723-CC88 (n = 1), t6238-CC8 (n = 1), and untypeable-CC8 (n = 1). A high percentage agreement (>95%) and kappa coefficient (>0.60) was largely observed with antibiotic susceptibility testing and DNA microarray, indicating substantial agreement. Some antibiotic and virulence gene markers were associated with specific clones. The detection of the collagen-binding adhesion (cna) gene was unique for t037-CC8-MRSA while the enterotoxin gene cluster (egc) and staphylococcal complement inhibitor (scn) gene were identified with t045-CC5-MRSA. Moreover, the combination of genes encoding enterotoxins (entA, entB, entK, entQ) was noted with most of the CC8 isolates. The t045-CC5-MRSA clone was positive for the mercury resistance (mer) operon. DNA microarray provides information on antibiotic resistance and virulence gene determinants and can be a useful tool to identify gene markers for specific S. aureus clones in Africa.

Structure-Antibacterial Activity Relationships of N-Substituted-(d-/l-Alaninyl) 1H-1,2,3-Triazolylmethyl Oxazolidinones.

Bacterial resistance towards the existing class of antibacterial drugs continues to increase, posing a significant threat to the clinical usefulness of these drugs. These increasing and alarming rates of antibacterial resistance development and the decline in the number of new antibacterial drugs' approval continue to serve as a major impetus for research into the discovery and development of new antibacterial agents. We synthesized a series of d-/l-alaninyl substituted triazolyl oxazolidinone derivatives and evaluated their antibacterial activity against selected standard Gram-positive and Gram-negative bacterial strains. Overall, the compounds showed moderate to strong antibacterial activity. Compounds 9d and 10d (d- and l-alaninyl derivatives bearing the 3,5-dinitrobenzoyl substituent), 10e (l-alaninyl derivative bearing the 5-nitrofurancarbonyl group) and 9f and 10f (d- and l-alaninyl derivatives bearing the 5-nitrothiophene carbonyl moiety) demonstrated antibacterial activity (MIC: 2 µg/mL) against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Moraxella catarrhalis standard bacterial strains. No significant differences were noticeable between the antibacterial activity of the d- and l-alaninyl derivatives as a result of the stereochemistry of the compounds.

Characterization of a CC1153 PVL-producing community-acquired methicillin-resistant Staphylococcus aureus from a dog bite wound.

The isolation of a rare community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strain from an infected dog bite wound is here reported. A 27-year old man presented with a deep open wound on his right hand caused by his dog's bite at the outpatient clinic of Infectious Disease Hospital (IDH), Kuwait. A wound swab was obtained for bacteriological culture and susceptibility testing. The wound culture yielded pure heavy growth of an MRSA isolate, designated IDH70, which was susceptible to vancomycin, teicoplanin, erythromycin, clindamycin, trimethoprim, fusidic acid and rifampicin. The patient was successfully treated with a combination of rifampicin and cotrimoxazole twice daily for 10 days. Molecular characterization revealed that IDH70 was positive for genes encoding Panton-Valentine leucocidin. IDH70 also carried the SCCmec V genetic element, belonged to coagulase type XIIIa, spa type t903, and was assigned to clonal complex 1153 and sequence type ST1153 (ST1153-V-t903). The report highlights the increasing burden of CA-MRSA in the community and the risk of its acquisition from bites of companion animals.

Antimycobacterial Activities of Novel 5-(1H-1,2,3-Triazolyl)Methyl Oxazolidinones.

The antibacterial activities of a series of triazolyl oxazolidinones against Mycobacterium tuberculosis strain in vitro and in vivo in a mice model are presented. Most active compounds were noncytotoxic against VERO cells with acceptable selectivity indexes (SI) as measures of compound tolerability. Structure activity relationships (SARs) revealed that analogs with alkylcarbonyl (IC(90): < 0.2 to 0.422 µg/mL) and arylcarbonyl (IC(90): < 0.2 to 2.103 µg/mL) groups at the piperazine 4N-position-displayed potent antimycobacterium activities, comparable to the methanesulfonyl (IC(90): < 0.2 µg/mL) analog, linezolid (IC(90): < 0.2 µg/mL), and isoniazid (IC(90): < 0.034 µg/mL). The furanylcarbonyl derivative also displayed potent activity, while the arylsulfonyl analogs were inactive. Of the triazolyl oxazolidinones, the morpholino (PH-27) derivative with medium bioavailability in plasma was most active in vivo, but relatively less efficacious than isoniazid.

The effect of systematic structural modifications on the antibacterial activity of novel oxazolidinones.

A novel series of tetraethylene glycol (TEG) triazolyl and squaramide containing oxazolidinones were synthesized and tested for their antibacterial activity against a selected panel of Gram-positive and Gram-negative bacteria. The 4-TEG-triazolyl derivatives were prepared by 'click reaction'. The introduction of the TEG and squaramide groups did not favor antibacterial activity. The three nucleoside-containing oxazolidinones were also prepared by 'click' methodology resulted in weak antibacterial activity.