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Uncontrolled bleeding and bacterial infections are major causes of wounds that do not heal. However, developing a wound plaster that can stop bleeding, resist blood extravasation, and realize directional transportation of drugs to promote wound healing remains a significant challenge. This study developed a superhydrophilic/hydrophobic PVA/CS/Ag@TPU Janus membrane with structural and wettability gradients. Water is absorbed from blood via the superhydrophilic layer attached to the wound and charge interactions between introduced chitosan (CS) and platelets promote blood clotting. The capillary pressure resistance (∆p > 0) from the superhydrophilic layer to the hydrophobic layer can prevent blood from permeating, reducing blood loss. A favorable ∆p ( < 0 ) based on structural and wettability gradients can realize the directional transportation of drugs that promote wound healing from the hydrophobic to superhydrophilic layer. The incorporation of CS and Ag endows Janus wound plaster with intrinsic antibacterial activity (99.9%). The bacterial antiadhesion capability of wound plaster can be achieved due to the resisting effect of the hydrated layer that formed on the hydrophilic layer, its low adhesion, and antibacterial capability. Experiments on mice with full-thickness skin defects showed that the wound-healing rate using the Janus membrane after dosing with a drug increased from 87.65% (without the drug) to approximately 100%. Moreover, it could accelerate wound healing, regenerate epidermal and granulation tissue, promote collagen formation, and reduce the scar area. This gradient-design strategy opens an avenue for next-generation wound dressings.

Introduction Diabetic foot ulcer infection (DFI) is an infectious disease of the skin and soft tissue in diabetics notorious for making rapid progress and being hard to cure. Staphylococcus aureus (S. aureus), most frequently detected in DFI, recently was suggested as an intracellular pathogen that can invade and survive within mammalian host cells. Autophagy in macrophages plays a vital immune role in combating intracellular pathogens through bacterial destruction, but there is a lack of empirical research about the infection characteristics and autophagy in diabetic skin infection. Methods Here, we used streptozotocin‐induced Sprague Dawley rats as a diabetic skin wound model to examine the S. aureus clearance ability and wound healing in vitro. Western blot and immunofluorescence staining were used to evaluate the autophagic flux of the macrophages in diabetic rats dermis, even with S. aureus infection. Results We demonstrated that infections in diabetic rats appeared more severe and more invasive with weakened pathogen clearance ability of the host immune system, which coincided with the suppressed autophagic flux in dermal macrophages, featured by a significant increase in endogenous LC3II/I and in p62. Conclusions Our results first provided convincing evidence that autophagy of macrophages was dysfunctional in diabetes, especially after being infected by S. aureus, which weakens the intracellular killing of S. aureus, potentially worsens the infections, and accelerates the infection spread in the diabetic rat model. Further understanding of the special immune crosstalk between diabetes host and S. aureus infection through autophagic factors will help to explain the complex clinical phenomenon and guarantee the development of effective therapies for diabetic foot infections., Infections in diabetic rats appeared more severe and more invasive with weakened pathogen clearance ability of the host immune system, which coincided with the suppressed autophagic flux in dermal macrophages, featured by a significant increase in endogenous LC3II/I and in p62. Our results provided convincing evidence that autophagy of macrophages was dysfunctional in diabetes, especially after being infected by Staphylococcus aureus (S. aureus), which weakens the intracellular killing of S. aureus, potentially worsen the infections, and accelerates the infection spread in the diabetic rat model.

Antimicrobial peptides (AMPs) have emerged as promising alternatives of traditional antibiotics against drug-resistant bacteria owing to their broad-spectrum antimicrobial properties and low tendency to drug resistance. However, their therapeutic efficacy in vivo, especially for infections in deep organs, is limited owing to their systemic toxicity and low bioavailability. Nanoparticles-based delivery systems offer a strategy to increase the therapeutic index of AMPs by preventing proteolysis, increasing the accumulation at infection sites, and reducing toxicity. Herein, we will discuss the current progress of using nanoparticles as delivery vehicles for AMPs for the treatment of deep infections.Statement of significanceAntimicrobial peptides (AMPs) are rarely directly used to treat deep infections due to their systemic toxicity and low bioavailability. This review summarizes recent progress that researchers employed nanoparticles-based delivery systems to deliver AMPs for the treatment of deep infections. Nanoparticles-based delivery systems offer a strategy to increase the therapeutic index of AMPs by preventing proteolysis, increasing the accumulation at infection sites, and reducing toxicity. Especially, the development of intelligent nanocarriers can achieve selective activation and active target in the infectious sites, thus improving the therapeutic efficacy against bacterial infection and reducing the toxicity against normal tissues.

In recent years, various research on cancer treatment has achieved significant progress. However, some of these treatments remain disputable because of the emergence and development of drug resistance, and the toxic side effects that were brought about by the lack of selectivity displayed by the treatments. Hence, there is considerable interest in a new class of anticancer molecules that is currently still under investigation termed the cationic antimicrobial peptides (AMPs). AMPs are a group of pervasive components of the innate immunity which can be found throughout all classes of life. The small innate peptides cover a broad spectrum of antibacterial activities due to their electrostatic interactions with the negatively charged bacterial membrane. Compared with normal cells, cancer cells have increased proportions of negatively charged molecules, including phosphatidylserine, glycoproteins, and glycolipids, on the outer plasma membrane. This provides an opportunity for exploiting the interaction between AMPs and negatively charged cell membranes in developing unconventional anticancer strategies. Some AMPs may also be categorized into a group of potential anticancer agents called cationic anticancer peptides (ACPs) due to their relative selectivity in cell membrane penetration and lysis, which is similar to their interaction with bacterial membranes. Several examples of ACPs that are used in tumor therapy for their ability in penetrating or lysing tumor cell membrane will be reviewed in this paper, along with a discussion on the recent advances and challenges in the application of ACPs.

Bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are potentially life-threatening and an urgent threat to public health. The present study aims to clarify the characteristics of carbapenemase-encoding and virulent plasmids, and their interactions with the host bacterium. A total of 425 Kp isolates were collected from the blood of BSI patients from nine Chinese hospitals, between 2005 and 2019. Integrated epidemiological and genomic data showed that ST11 and ST307 Kp isolates were associated with nosocomial outbreak and transmission. Comparative analysis of 147 Kp genomes and 39 completely assembled chromosomes revealed extensive interruption of acrR by ISKpn26 in all Kp carbapenemase-2 (KPC-2)-producing ST11 Kp isolates, leading to activation of the AcrAB-Tolc multidrug efflux pump and a subsequent reduction in susceptibility to the last-resort antibiotic tigecycline and six other antibiotics. We described 29 KPC-2 plasmids showing diverse structures, two virulence plasmids in two KPC-2-producing Kp, and two novel multidrug-resistant (MDR)-virulent plasmids. This study revealed a multifactorial impact of KPC-2 plasmid on Kp, which may be associated with nosocomial dissemination of MDR isolates.

Staphylococcus aureus, a pathogen most frequently found in diabetic foot ulcer infection, was recently suggested as an intracellular pathogen. Autophagy in professional phagocytes like macrophages allows selective destruction of intracellular pathogens, and its dysfunction can increase the survival of internalized pathogens, causing infections to worsen and spread. Previous works have shown that S. aureus infections in diabetes appeared more severe and invasive, and coincided with the suppressed autophagy in dermal tissues of diabetic rat, but the exact mechanisms are unclear. Here, we demonstrated that accumulation of advanced glycation end products (AGEs) contributed to the diminished autophagy-mediated clearance of S. aureus in the macrophages differentiated from PMA-treated human monocytic cell line THP-1. Importantly, infected macrophages showed increased S. aureus containing autophagosome, but the subsequent fusion of S. aureus containing autophagosome and lysosome was suppressed in AGEs-pretreated cells, suggesting AGEs blocked the autophagic flux and enabled S. aureus survival and escape. At the molecular level, elevated lysosomal ARL8 expression in AGEs-treated macrophages was required for AGEs-mediated inhibition of autophagosome-lysosome fusion. Silencing ARL8 in AGEs-treated macrophages restored autophagic flux and increased S. aureus clearance. Our results therefore demonstrate a new mechanism, in which AGEs accelerate S. aureus immune evasion in macrophages by ARL8-dependent suppression of autophagosome-lysosome fusion and bactericidal capability.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections have become a major global public health challenge. Disinfectants play an important role in controlling horizontal transmission in healthcare facilities. However, the long and extensive routine use of disinfectants, and far less regulated, leading to concern about the development of disinfectant resistance. We detected the susceptibility of CRKP strains against seven kinds of disinfectants commonly used in clinic to guide and assist the infection control work in hospital. Methods: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests of seven kinds of disinfectants (0.1% benzalkonium bromide, 4% aqueous chlorhexidine, 75% alcohol, entoiodine II, 2% glutaraldehyde, 2000mg/L chlorine-containing disinfectants and 3% hydrogen peroxide) were detected by broth dilution method. Three efflux pump genes (oqxA、oqxB、and qacE△1-sul1) were detected by PCR. Results: A total of 162 strains of non-repetitive CRKP strains were isolated in SYS Memorial Hospital from 2015 to 2019. The MBCs expressed by diluted multiples of 64 CRKP strains against the seven kinds of disinfectants were 1-128, 16-32768, 2-64, 16-4096, 4-64, 2-8 and 64-2048, respectively. Aqueous chlorhexidine should be ≥ 2.5 g/L when rinsing or gargling mucous membrane and wound, 0.1% benzalkonium bromide should avoided be diluted, and chlorine-containing disinfectants should be ≥ 1000 mg/L. The mean MIC value of aqueous chlorhexidine from intensive care unit (ICU) (0.0034%) was significantly higher than that from non-ICU (0.0019%) (p < 0.05). The positive rates of three efflux pump genes oqxA, oqxB and qacE△1-sul1 were 68.8% (44/64), 15.6% (10/64) and 89.1% (57/64), respectively.Conclusion: The CRKP strains isolated showed extensive resistance to clinically used disinfectants, and the concentration of aqueous chlorhexidine and chlorine-containing disinfectants needs to be increased compared with the current standards of the healthcare industry. It reminds us to strengthen the monitoring of disinfectant resistance to super drug-resistant bacteria.

The emergence and transmission of the mobile colistin resistance gene (mcr-1) threatened the extensive use of polymyxin antimicrobials. Accumulated evidence showed that the banning of colistin additive in livestock feed efficiently reduce mcr-1 prevalence, not only in animals but also in humans and environments. However, our previous study has revealed that a small proportion of Escherichia coli could continually carry chromosomally-encoded mcr-1. The chromosomally-encoded events, indicated the existence of stabilized heritage of mcr-1 and revealed a potential threat in the antimicrobial stewardship interventions, are yet to be investigated. In this study, we systematically investigated the genetic basis of chromosomally-encoded mcr-1 in prevalence and potential mechanisms of lineage, plasmid, insertion sequence, and phage. Our results demonstrated that the emergence of chromosomally-encoded mcr-1 could originate from multiple mechanisms, but mainly derived through the recombination of ISApl1/Tn6330. We reported a specific transmission mechanism, which is a phage-like region without lysogenic components, could associate with the emergence and stabilization of chromosomally-encoded mcr-1. These results highlighted the potential origin and risks of chromosomally-encoded mcr-1, which could be a heritable repository and thrive again when confronted with new selective pressures. To the best of our knowledge, this is the first study to systematically reveal the genomic basis of chromosomally-encoded mcr-1, and report a specific transmission pattern involved in phage-like region. Overall, we demonstrate the origin mechanisms and risks of chromosomally-encoded mcr-1. It highlights the need of public attention on chromosome-encoded mcr-1 to prevent from its reemergence.

Additional file 1: Table S1.

Additional file 3: Figure S2. Flow diagram of the study selection process.

This study aimed to describe the clinicopathologic characteristics of non-puerperal mastitis and to investigate spectrum of organisms causing it in the population of Southern China. We retrospectively registered 364 female patients with histological confirmation of inflammatory disease of the breast in the non-lactational phase, who were admitted to our institution over an 11-year period (2005-2016). Clinical, laboratory, and radiographic imaging features, as well as their bacteriological etiology, were analyzed in detail. In this study, 117 patients were diagnosed with periductal mastitis (PDM)/mammary duct ectasia (MDE) and 247 patients were diagnosed with idiopathic granulomatous mastitis (IGM). There were significant differences in terms of mean age of onset, menstruation period, and menstruation history. Nipple discharge, inverted nipple, and the ratio of abscess and fistula were more spontaneous in women with PDM/MDE compared to IGM. The inflammatory biomarkers including leukocyte count, neutrophil percentage, and high-sensitivity C-reactive protein in PDM/MDE group were significantly higher than IGM group. For bacteriological etiology, the most commonly isolated organism was Corynebacterium kroppenstedtii (C kroppenstedtii) in the IGM group and Staphylococcus in the PDM/MDE group. The study shows that the combination of demographic characteristics and clinicopathological characteristics was helpful in differential diagnosis of PDM/MDE and IGM. IGM can be associated with C kroppenstedtii, providing a possible effective therapeutic and preventive method by targeting this kind of bacilli. Key words: bacteriological etiology; breast disease; idiopathic granulomatous mastitis; mammary ductectasia; periductal mastitis

Background Cardiobacterium is a fastidious Gram-negative bacillus, and is a rare human pathogen in clinical settings. Herein, we describe a case of Cardiobacterium valvarum (C. valvarum) endocarditis with a rare complication of cerebral hemorrhage after mitral valve replacement (MVR), tricuspid valve prosthesis (TVP) and vegetation removal operation. Case presentation A 41-year-old woman who had a history of gingivitis developed into infective endocarditis due to the infection of C. valvarum. Then, she was hospitalized to receive MVR, TVP and vegetation removal operation. The indicators of patient tended to be normal until the abrupt cerebral hemorrhage occurred on day 15 after operation. This is the first well-described case of C. valvarum infection in China, and the first report of C. valvarum endocarditis with cerebral hemorrhage after MVR, TVP and vegetation removal operation worldwide. Conclusions We reported the first case of C. valvarum infection in China clinically, with a rare complication of cerebral hemorrhage after MVR, TVP and vegetation removal operation.

miR-34a is significantly down-regulated in breast cancer tissues and cell lines, which may be correlated with breast cancer multi-drug resistance (MDR). Here, we conducted cell-based experiments and clinical studies in a cohort of 113 breast cancer samples to analyze miR-34a expression and breast cancer MDR. Expression of miR-34a is down-regulated in the multi-drug resistant MDR-MCF-7 cells compared with its parental cells. Patients with miR-34a low expression had poorer overall survival (OS) and disease free survival (DFS) in comparison with those with high expression. Transfecting miR-34a mimics into MDR-MCF-7 breast cancer cells led to partial MDR reversal. Compared with the control group, miR-34a significantly reduced both the mRNA and protein expressions of BCL-2, CCND1 and NOTCH1, but no obvious changes were found in P53 or TOP-2a expression. In breast cancer tissue samples, the expression of miR-34a was related to BCL-2, CCND1 and NOTCH1, but not to HER-2, P53 and TOP-2a. Altogether, our findings suggest that miR-34a is an MDR and prognosis indicator of breast cancer, which may participate in the regulation of drug-resistant breast cancer by targeting BCL-2, CCND1, and NOTCH1.

Table S2. The resistance rate to 14 antibiotics of 87Â S. aureus isolates. (DOCX 20 kb)

Table S1. Spa types and genetic characteristics of select S. aureus isolates recovered from medical laboratory staff. (DOCX 26 kb)

Current clinical treatment of Helicobacter pylori infection, the main etiological factor in the development of gastritis, gastric ulcers, and gastric carcinoma, requires a combination of at least two antibiotics and one proton pump inhibitor. However, such triple therapy suffers from progressively decreased therapeutic efficacy due to the drug resistance and undesired killing of the commensal bacteria due to poor selectivity. Here, we report the development of antimicrobial polypeptide-based monotherapy, which can specifically kill H. pylori under acidic pH in the stomach while inducing minimal toxicity to commensal bacteria under physiological pH. Specifically, we designed a class of pH-sensitive, helix–coil conformation transitionable antimicrobial polypeptides (HCT-AMPs) (PGA) m - r -(PHLG-MHH) n , bearing randomly distributed negatively charged glutamic acid and positively charged poly(γ-6- N -(methyldihexylammonium)hexyl-l-glutamate) (PHLG-MHH) residues. The HCT-AMPs showed unappreciable toxicity at physiological pH when they adopted random coiled conformation. Under acidic condition in the stomach, they transformed to the helical structure and exhibited potent antibacterial activity against H. pylori , including clinically isolated drug-resistant strains. After oral gavage, the HCT-AMPs afforded comparable H. pylori killing efficacy to the triple-therapy approach while inducing minimal toxicity against normal tissues and commensal bacteria, in comparison with the remarkable killing of commensal bacteria by 65% and 86% in the ileal contents and feces, respectively, following triple therapy. This strategy renders an effective approach to specifically target and kill H. pylori in the stomach while not harming the commensal bacteria/normal tissues.

Background Medical laboratory staff are a high-risk population for colonization of Staphylococcus aureus (S. aureus) due to direct and dense contact with the pathogens; however, there is limited information about this colonization. This study sought to determine the prevalence and molecular characteristics of nasal colonization by S. aureus in medical laboratory staff in Guangzhou, southern China, and to compare the differences between microbiological laboratory (MLS) and non-microbiological laboratory (NMLS) staff. Methods S. aureus colonization was assessed by nasal swab cultures from 434 subjects, including 130 MLSs and 304 NMLSs from 33 hospitals in Guangzhou. All S. aureus isolates underwent the antimicrobial susceptibility test, virulence gene detection and molecular typing. Results The overall prevalence of S. aureus carriage was 20.1% (87/434), which was higher in MLSs than in NMLSs (26.2% vs. 17.4%, P

Background The nasal cavity is the main colonization site of Staphylococcus aureus (S. aureus) in human body. Nasal carriage may be a strong risk factor for some serious infection. There was still limited information about the nasal carriage for S. aureus in south China. Methods Sought to determine the prevalence and molecular characteristics of S. aureus nasal carriage, 295 volunteers residing on a medicine campus were investigated and sampled the nasal cavity swab. Selected S. aureus isolates were carried through molecular analysis, including pulsed-field gel electrophoresis (PFGE), multilocus sequence analysis, staphylococcal cassette chromosome mec (SCCmec) and virulence gene detection. Results A total of 73 S. aureus isolates were recovered from separate subjects (24.7%, 73/295), with one methicillin-resistant S. aureus (MRSA) isolate (0.3%, 1/295). Among the 73 isolates, 71 isolates were successfully grouped into 13 pulsotypes by PFGE analysis, with profiles A and L the most prevalent; 12 sequence types (STs) were found among the 23 isolates which had similar drug resistant spectrum. ST59, ST188 and ST1 were the most prevalent, accounting for 17.4, 13.0 and 13.0% of all isolates, respectively. The MRSA isolate presented ST8-SCCmec III. 56.5% of isolates carried both the staphylococcal enterotoxin A (sea) and enterotoxin B (seb) genes. 83.6% of the S. aureus isolates were resistant to penicillin, all isolates were susceptible to quinupristin/dalfopristin, levofloxacin, teicoplanin and vancomycin. The most common risk factors for S. aureus carriage were being male, age ≤30 years, and nasal cavity cleaning habits. Conclusions Colonization by S. aureus was greater among male and young age (20–30 years) students and those with irregularity nasal cleaning. The S. aureus isolates selected were revealed into various sequence types and pulsotypes, indicating molecular heterogeneity among S. aureus isolates from the populations in the medical college in Guangzhou.

Objective. To understand the bacterial profile and antibiotic resistance patterns in diabetic foot infection (DFI) in different Wagner’s grades, IDSA/IWGDF grades, and different ulcer types in Guangzhou, in order to provide more detailed suggestion to the clinician about the empirical antibiotic choice. Methods. 207 bacteria were collected from 117 DFIs in Sun Yat-sen Memorial Hospital from Jan.1, 2010, to Dec.31, 2015. The clinical data and microbial information were analyzed. Results. The proportion of Gram-negative bacteria (GNB) was higher than Gram-positive bacteria (GPB) (54.1% versus 45.9%), in which Enterobacteriaceae (73.2%) and Staphylococcus (65.2%) were predominant, respectively. With an increasing of Wagner’s grades and IDSA/IWGDF grades, the proportion of GNB bacterial infection, especially Pseudomonas, was increased. Neuro-ischemic ulcer (N-IFU) was more susceptible to GNB infection. Furthermore, with the aggravation of the wound and infection, the antibiotic resistance rates were obviously increased. GPB isolated in ischemic foot ulcer (IFU) showed more resistance than the N-IFU, while GNB isolates were on the opposite. Conclusions. Different bacterial profiles and antibiotic sensitivity were found in different DFU grades and types. Clinician should try to stay updated in antibiotic resistance pattern of common pathogens in their area. This paper provided them the detailed information in this region.

Agarose gel image of virulence factor genes of partial positive strains in the 62 MRSA isolates. (A ~ M), Virulence factor genes detected by PCR. Marker refers to DNA marker (100 bp ladder); # numbers, isolate number; Sea ~ seo, staphylococcal enterotoxins A ~ O gene; hla, α-hemolysin gene; hlb, β-hemolysin gene; hlg, γ-hemolysin gene; tsst-1,toxic shock syndrome toxin 1 gene; PVL, Panton-Valentine leukocidin gene ; PCR, polymerase chain reaction. (PDF 280 kb)

Genetic relatedness among the 60 MRSA strains. Phylogenetic relationships were obtained by PFGE. Cluster analysis was performed with the software program BioNumerics 5.0 (Maths, Belgium) using the Dice coefficient and the unweighted pair group method(UPGMA). The isolates with the similarity over 75Â % were clustered in patterns. PFGE, pulsed-field gel electrophoresis; CA/HA, community-acquired MRSA or hospital-acquired MRSA; PVL, Panton-Valentine leukocidin gene; SCCmec, staphylococcal cassette chromosome mec; MLST, multilocus sequence typing; +, positive. (PDF 24Â kb)

The antibiotic resistance of 62 methicillin-resistant S. aureus isolates. Table S2. The SCCmec type distribution of CA-MRSA and HA-MRSA. Table S3. MLST type distribution of CA-MRSA and HA-MRSA. Table S4. SCCmec type and MLST type distribution of 62 MRSA isolates. (PDF 202Â kb)

Combination of two or more therapeutic strategies with different mechanisms can cooperatively prohibit cancer development. Combination of chemotherapy and small interfering RNA (siRNA)-based therapy represents an example of this approach. Hypothesizing that the chemotherapeutic drug and the siRNA should be simultaneously delivered to the same tumoral cell to exert their synergistic effect, the development of delivery systems that can efficiently encapsulate two drugs and successfully deliver payloads to targeted sites via systemic administration has proven to be challenging. Here, we demonstrate an innovative "two-in-one" micelleplex approach based on micellar nanoparticles of a biodegradable triblock copolymer poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(2-aminoethyl ethylene phosphate) to systemically deliver the siRNA and chemotherapeutic drug. We show clear evidence that the micelleplex is capable of delivering siRNA and paclitaxel simultaneously to the same tumoral cells both in vitro and in vivo. We further demonstrate that systemic administration of the micelleplex carrying polo-like kinase 1 (Plk1) specific siRNA and paclitaxel can induce a synergistic tumor suppression effect in the MDA-MB-435s xenograft murine model, requiring a thousand-fold less paclitaxel than needed for paclitaxel monotherapy delivered by the micelleplex and without activation of the innate immune response or generation of carrier-associated toxicity.

The main aim of this study was to understand the relationship between the drug-resistant characteristics of Klebsiella pneumoniae and CTX-M-type extended spectrum β-lactamases (ESBLs), and to detect the distributions of CTX-M-type ESBLs in clinically isolated strains. CTX-M ESBL genes isolated from the clinical samples were amplified by polymerase chain reaction and identified by sequence analysis; the antibiotic susceptibility of the samples was determined using the Kirby-Bauer disc-diffusion method. One hundred and five strains among the 246 isolated strains of K. pneumoniae tested positive for ESBL production (42.68%); 92 of these produced CTX-M ESBLs. Of the 92 CTX-M ESBL strains, 81 produced CTX-M-1 ESBLs and 11 produced CTX-M-25 ESBLs. Fifty-seven of the CTX-M-1 ESBL- and six of the CTX-M-25 ESBL-producing bacteria had CTX-M ESBL genes that coexisted in the plasmid and chromosome. The Kirby-Bauer antibiotic susceptibility method revealed that CTX-M ESBL-positive strains showed a higher rate of resistance to cefazolin, cefoxitin, cefuroxime, ceftazidime, cefotaxime, aztreonam, levofloxacin, and cotrimoxazole, compared to the CTX-M ESBL-negative strains (P < 0.05). The CTX-M ESBL genes were commonly observed in the K. pneumoniae isolated from respiratory tract samples; these were significantly associated with the drug-resistant characteristics of K. pneumoniae to β-lactam antibiotics.

Background Streptococcus pneumoniae infections are a major cause of global morbidity and mortality, and the emergence of antibiotic-resistant Streptococcus pneumoniae strains has been increasingly reported. This study provides up-to-date information on bacterial serotype distribution and drug resistance from S. pneumoniae clinical isolates that could guide prevention and treatment strategies for pneumococcal disease in China. Methods A total of 94 S. pneumoniae isolates were collected from outpatients and inpatients at one Chinese hospital from 2011–2013. Drug susceptibility and resistance was determined by minimum inhibitory concentrations (MICs). Capsular serotypes were identified by the quellung reaction test and multiplex polymerase chain reaction. Results Fifteen serotypes were identified among the 94 S. pneumoniae clinical isolates that were collected. Prevalent serotypes were 19F (42.6 %), 19A (8.5 %), 3 (8.5 %), and 6B (7.4 %). Potential immunization coverage rates for the 7-, 10- and 13-valent pneumococcal polysaccharide conjugate vaccines were 59.6, 62.6, and 79.6 %, respectively. Resistance rates to tetracycline, erythromycin, and trimethoprim/sulfamethoxazole were 91.2, 80.2 and 63.8 %, respectively. Resistance rates to penicillin, amoxicillin, ceftriaxone, and cefotaxime were 47.3, 34.1, 19.8, and 18.7 %, respectively. In almost all cases, antimicrobial resistance of the S. pneumoniae isolates in patients five years or younger was higher than isolates collected from patients aged 51 years or older. Conclusion Prevalent serotypes among the 94 S. pneumoniae clinical isolates were 19F, 19A, 3, and 6B. The 13-valent pneumococcal polysaccharide conjugate vaccine covered the majority of the serotypes identified in this sample. Drug resistance varied among different serotypes and age groups. Clinical precautions should be taken to avoid the development of multidrug resistance in this potential human pathogen. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-1042-5) contains supplementary material, which is available to authorized users.

Background The pathogenic potential and commensal nature of Staphylococcus aureus allows for easy transmission both within and outside of the hospital environment, and nasal carriage may be responsible for some serious infections. This study aimed to determine the molecular and epidemiological characteristics of nasal colonization by S. aureus in community residents (CR) and healthcare workers (HW) at Sun Yat-Sen University, Guangzhou, China. Methods A total of 589 volunteers, both CR (n = 297) and HW (n = 292), were recruited. Each subject completed a questionnaire, and specimens were obtained from the anterior nares for S. aureus screening. Genotypic analysis included pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, and virulence gene detection. Results A total of 138 S. aureus isolates were recovered from separate subjects (23.4 %, 138/589), with four isolates showing methicillin resistance (0.7 %, 4/589). The prevalence of S. aureus carriage was 25.3 % (75/297) in CR and 21.6 % (63/292) in HW. Methicillin-resistant S. aureus (MRSA) were isolated from one CR (0.3 %, 1/297) and three HW (1.0 %, 3/292). The most common risk factors for S. aureus carriage in CR were being male, age ≤ 30 years, and nasal cavity cleaning habits. Having a household member in the healthcare profession was associated with increased risk among HW. Sequence type (ST)188 and ST59 were the most prevalent among the 20 observed STs, accounting for 14.6 % and 12.2 % of all isolates, respectively. The four MRSA isolates presented four different STs, with one isolate carrying a type IVa SCCmec element and the other three isolates containing type III SCCmec. PFGE analysis grouped the 129 isolates into 23 pulsotypes, with profiles A, N, E, L, and O the most prevalent. The Panton-Valentine leucocidin gene (pvl) was identified in two of the 138 isolates, while 57.5 % of isolates carried both the Staphylococcus aureus enterotoxin A (sea) and enterotoxin B (seb) genes. Conclusions These data indicate a low prevalence of nasal MRSA carriage but evidence of molecular heterogeneity among S. aureus isolates from CR and HW at Sun Yat-Sen University, Guangzhou. Differences in epidemiological and molecular characteristics of S. aureus between CR and HW populations may be useful for the understanding and prevention of S. aureus infection. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-1032-7) contains supplementary material, which is available to authorized users.

List of primers used for S. pneumonia serotype deduction ( http://www.cdc.gov/streplab/pcr.html ). Table S2. Distribution of serotypes in different specimens. Table S3. Distribution of different serotypes in different age groups. Table S4. The serotypes distribution and coverage rates of vaccines of the 94 isolates of S.pneumoniae. Table S5. The serotype distribution and coverage rates of vaccines of S.pneumoniae isolates from children and elderly patients. Table S6. The antibiotic susceptibility of 94 strains of S.pneumoniae. (PDF 140 kb)

A major obstacle to developing small interfering RNAs (siRNAs) as cancer drugs is their intracellular delivery to disseminated cancer cells. Fusion proteins of single-chain fragmented antibodies (ScFvs) and positively charged peptides deliver siRNAs into specific target cells. However, the therapeutic potential of ScFv-mediated siRNA delivery has not been evaluated in cancer. Here, we tested whether Polo-like kinase 1 (PLK1) siRNAs complexed with a Her2-ScFv-protamine peptide fusion protein (F5-P) could suppress Her2(+) breast cancer cell lines and primary human cancers in orthotopic breast cancer models. PLK1-siRNAs transferred by F5-P inhibited target gene expression, reduced proliferation, and induced apoptosis of Her2(+) breast cancer cell lines and primary human cancer cells in vitro without triggering an interferon response. Intravenously injected F5-P/PLK1-siRNA complexes concentrated in orthotopic Her2(+) breast cancer xenografts and persisted for at least 72 hours, leading to suppressed PLK1 gene expression and tumor cell apoptosis. The intravenously injected siRNA complexes retarded Her2(+) breast tumor growth, reduced metastasis, and prolonged survival without evident toxicity. F5-P-mediated delivery of a cocktail of PLK1, CCND1, and AKT siRNAs was more effective than an equivalent dose of PLK1-siRNAs alone. These data suggest that F5-P could be used to deliver siRNAs to treat Her2(+) breast cancer.

The chemokine receptor CXCR4 and its ligand CXCL12 have been shown to mediate the metastasis of many malignant tumors including breast carcinoma. Interaction between hepatocyte growth factor (HGF) and the Met receptor tyrosine kinase mediates development and progression of cancers. HGF is able to induce CXCR4 expression and contributes to tumor cell invasiveness in breast carcinoma. However, the mechanism of the CXCR4 expression modulated by c-Met-HGF axis to enhance the metastatic behavior of breast cancer cells is still unclear. In this study, we found that HGF induced functional CXCR4 receptor expression in breast cancer cells. The effect of HGF was specifically mediated by PKCζ activity. After transfection with PKCζ-siRNA, the phosphorylation of PKCζ and CXCR4 was abrogated in breast cancer cells. Interference with the activation of Rac1, a downstream target of HGF, prevented the HGF-induced increase in PKCζ activity and CXCR4 levels. The HGF-induced, LY294002-sensitive translocation of PKCζ from cytosol to plasma membrane indicated that HGF was capable of activating PKCζ, probably via phosphoinositide (PI) 3-kinases. HGF treatment also increased MT1-MMP secretion. Inhibition of PKCζ, Rac-1 and phosphatidylinositol 3-kinase may attenuate MT1-MMP expression in cells exposed to HGF. Functional manifestation of the effects of HGF revealed an increased ability for migration, chemotaxis and metastasis in MDA-MB-436 cells in vitro and in vivo. Our findings thus provided evidence that the process of HGF-induced functional CXCR4 expression may involve PI 3-kinase and atypical PKCζ. Moreover, HGF may promote the invasiveness and metastasis of breast tumor xenografts in BALB/c-nu mice via the PKCζ-mediated pathway, while suppression of PKCζ by RNA interference may abrogate cancer cell spreading.

The P2X7 receptor regulates cell growth through mediation of apoptosis. Low level expression of P2X7 has been linked to cancer development because tumor cells harboring a defective P2X7 mechanism can escape P2X7 pro-apoptotic control. microRNAs (miRNAs) function as negative regulators of post-transcriptional gene expression, playing major roles in cellular differentiation, proliferation, and metastasis. In this study, we found that miR-150 was over-expressed in breast cancer cell lines and tissues. In these breast cancer cell lines, blocking the action of miR-150 with inhibitors leads to cell death, while ectopic expression of the miR-150 results in increased cell proliferation. We deploy a microRNA sponge strategy to inhibit miR-150 in vitro, and the result demonstrates that the 3'-untranslated region (3'UTR) of P2X7 receptor contains a highly conserved miR-150-binding motif and its direct interaction with miR-150 down-regulates endogenous P2X7 protein levels. Furthermore, our findings demonstrate that miR-150 over-expression promotes growth, clonogenicity and reduces apoptosis in breast cancer cells. Meanwhile, these findings can be decapitated in nude mice with breast cancer xenografts. Finally, these observations strengthen our working hypothesis that up-regulation of miR-150 in breast cancer is inversely associated with P2X7 receptor expression level. Together, these findings establish miR-150 as a novel regulator of P2X7 and a potential therapeutic target for breast cancer.