Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a severe health threat to human beings; however, the epidemic and molecular characteristics exist along with the change in the geographic environment and genealogy. Jiangxi province is located in southeast China, which is a high-MDR-TB burden area. Rifampin (RIF) and isoniazid (INH) are the most important first-line anti-tuberculosis drugs. The major drug target genes include rpoB for RIF and katG , inhA , and ahpC for INH. To determine the frequency and distribution of mycobacterial mutations in these genes, we sequenced specific genes of M . tuberculosis that are associated with resistance to RIF and INH in 157 phenotypic MDR isolates. At the same time, RD105 DTM-PCR and 15 loci MIRU-VNTR were performed to demonstrate the genetic lineage. It was shown that the Beijing genotype was predominant (84.1%) among these strains. The results also showed mutations within the 81 bp core region of rpoB in 93.6% of strains and mutations in a structural gene ( katG ) and two regulatory regions (the promoter of inhA and intergenic region of oxyR-ahpC ) were shown in 88.5% of phenotypic MDR isolates. There were no significant differences in codon mutations between the Beijing and non-Beijing genotypes, as well as the clustered and no-clustered strains. The most prevalent mutations involved in RIF and INH were Ser531Leu in rpoB (55.4%) and Ser315Thr in KatG (56.1%), respectively. There was no significant difference in RIF and INH resistance between MDR-TB and other drug-resistant tuberculosis (DR-TB). The results demonstrated that some MDR-TB patients are predicted to have recent transmission.

BackgroundTo understand the relationship between the Staphylococcus aureus infection rate and the reasonable usage of antibiotics, which will help in the effective control of MRSA infection.MethodsAll data were obtained by the application of the nosocomial infection surveillance network. Drug resistance, departmental sources, and isolated sites as well as infection rate variations of S. aureus were analyzed in the 7-year period in key departments.ResultsBetween 2008 and 2014, 2525 strains of S. aureus isolates, mainly from sputum, skin/soft tissue, bloodstreams were collected from several hospital departments including respiratory, burn, brain surgery, orthopedics, ICU, and emergency. During these periods, the resistance rate of S. aureus to most drugs, including oxacillin, tetracycline, erythromycin, clindamycin, gentamicin, and ciprofloxacin, showed a tendency to decrease. The resistance to sulphamethoxazole/trimethoprim showed the opposite trend (P = 0.075) and there were no S. aureus strains resistant to linezolid and vancomycin. The MRSA infection rate was different across crucial hospital departments, with the burns department and ICU maintaining a high infection level. Over the 7-year period, both the brain surgery and the emergency departments had an expected upward trend (P < 0.05), while the orthopedic department showed a clear downward trend (P < 0.05) in MRSA infection rate.ConclusionHospitals should continue to maintain the current pattern of antibiotic administration, while more effective measures should be taken to reduce the high MRSA infection rate in some important hospital departments.

BackgroundS.aureus is a predominant pathogen that causes infection in critically ill patients, but little information exists regarding the characterization of S. aureus from different sources in burn patients in southeastern China.MethodsWe enrolled 125 patients with S. aureus infection in burns center between Jan 2014 and Dec 2015. S. aureus isolates were characterized by antimicrobial susceptibility test, toxin gene detection, and molecular typing with multilocus sequence type, staphylococcal protein A (spa) type, and staphylococcal cassette chromosome mec (SCCmec) type.ResultsSixty-eight MRSA were isolated from SSTI and 31 from non-SSTI patients, respectively. Overall, the drug-resistant ability of S. aureus isolated from SSTI was higher than that from non-SSTI groups. SCCmecIII-CC239-t030 was the most common clone (38 from SSTIs, and 8 from non-SSTIs). Seg was the most common enterotoxin gene (21 from SSTIs and 33 from non-SSTIs). Isolates from SSTIs was more likely to carry seb (P = 0.04), while those from non-SSTIs tended to carry sea and seg (P = 0.002 and 0.01, respectively). Although isolates carried four hemolysin genes, there was no significant difference between them (P > 0.05).ConclusionSCCmecIII-CC239-t030 was the most common clone in Jiangxi burns center, China. The molecular characterization of S. aureus was quite different between SSTI and non-SSTI groups.

Gramicidin S (GS), one of the most widely investigated antimicrobial peptides (AMPs), is known for its robust antimicrobial activity. However, it is restricted to topical applications due to undesired hemolytic activity. With the aim to obtain non-toxic GS analogues, we describe herein a molecular approach where the native GS β-turn region is replaced by synthetic β,γ-diamino acids (β,γ-DiAAs). Four β,γ-DiAA diastereomers were employed to mimic β-turn structure to afford GS analogues GS3-6 that exhibit diminished hemolytic activity. A comparative structural study demonstrates that the (βR,γS)-DiAA displays the most stable β-turn mimic. To further improve the therapeutic index (e.g. high antibacterial activity and low hemolytic activity) and to extend the molecular diversity, GS5 and GS6 were used as structural scaffolds to introduce additional hydrophobic or hydrophilic groups. We show that GS6K, GS6F and GS display comparable antibacterial activity while GS6K and GS6F possess significantly decreased toxicity. Moreover, antibacterial mechanism studies suggest that GS6K kills bacteria mainly through the disruption of membrane. Results and DiscussionScope of Lead Peptide Molecular Design and Synthesis. Initially, four diastereomeric GS analogues (GS3-6, Figure 1) were synthesized to evaluate in both biological and conformational aspects. The β,γ-DiAAs were prepared using the synthetic strategy previously described by our group starting from α-amino acids. [42] With respect to the aromatic character in the β-turn region, [36,39] D-and L-phenylalanine were chosen as starting materials (Scheme 1). Cbz-protected intermediates 7, 8, 9 and 10 were prepared as previously described. [23,43] Since the configuration of an analogue of compound 9 has been previously determined by crystallographic structure, [43] the other compounds could thereby be differentiated by the comparison of their NMR spectrum with their enantiomers. Noteworthy, the separation of the diastereomers is rather difficult when directly applying the silica gel chromatography. Alternatively, the minor diastereomers (8 and 10) can be easily precipitated in the presence of cold diethyl ether, and it consequently allows the major diastereomers (7 and 9) being purified by chromatography. To allow the solid phase synthesis, Cbz protecting group was further transferred to Fmoc protecting group (Scheme 1).Previous studies have demonstrated that GS and its analogues can be readily synthesized by solution-phase cyclization of the corresponding linear precursor peptides with protected side chains. [44] To this end, the linear precursors were assembled by following an either conventional or microwave-assistant solid phase Fmoc/tBu strategy. All Fmoc-protected α-amino acids are commercially available. Each projected peptide was assembled stepwise on the solid support starting from Fmoc-Pro-2-Chlorotrityl Chloride (CTC) Resin. During the sequential coupling, HBTU/HOBt (conventional synthesis) or HBTU (microwave-assistant synthesis) was used for activation, DiPEA as base,...

Introduction: With the widespread use of antibiotics and increasing number of immunocompromised patients, many rare bacterial infections have become increasing. Recently, only a few cases showed central nervous system (CNS) nocardiosis and Exiguobacterium bacteremia. However, the case that CNS nocardiosis together with Exiguobacterium bacteremia has never been reported. Case Presentation: The patient was admitted to a tertiary hospital with CNS infection symptoms. Cerebrospinal fluid and blood were both sent to culture. Pathogens were both isolated from cerebrospinal fluid and blood, following 16s rRNA sequencing, which were finally identified as Nocardia and Exiguobacterium species. Conclusions: It is the first reported case of CNS Nocardia terpenica infection in a patient without abscess formation in the CNS. Additionally, this patient also had a complex infection involving Exiguobacterium profundum bacteremia.