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Background The virulence role of surface antigens in a single serotype of Klebsiella pneumoniae strain have been studied, but little is known about whether their contribution will vary with serotype. Method To investigate the role of K and O antigen in hyper-virulent strains, we constructed O and K antigen deficient mutants from serotype K1 STL43 and K2 TSGH strains from patients with liver abscess, and characterized their virulence in according to the abscess formation and resistance to neutrophil phagocytosis, serum, and bacterial clearance in liver. Results Both of K1 and K2-antigen mutants lost their wildtype resistance to neutrophil phagocytosis and hepatic clearance, and failed to cause abscess formation. K2-antigen mutant became serum susceptible while K1-antigen mutant maintained its resistance to serum killing. The amount of glucuronic acid, indicating the amount of capsular polysaccharide (CPS, K antigen), was inversed proportional to the rate of phagocytosis. O-antigen mutant of serotype K1 strains had significantly more amount of CPS, and more resistant to neutrophil phagocytosis than its wildtype counterpart. O-antigen mutants of serotype K1 and K2 strains lost their wildtype serum resistance, and kept resistant to neutrophil phagocytosis. While both mutants lacked the same O1 antigen, O-antigen mutant of serotype K1 became susceptible to liver clearance and cause mild abscess formation, but its serotype K2 counterpart maintained these wildtype virulence. Conclusion We conclude that the contribution of surface antigens to virulence of K. pneumoniae strains varies with serotypes., Author(s): Kuo-Ming Yeh[sup.1,2] , Sheng-Kung Chiu[sup.1] , Chii-Lan Lin[sup.3,4] , Li-Yueh Huang[sup.5] , Yu-Kuo Tsai[sup.5] , Jen-Chang Chang[sup.5] , Jung-Chung Lin[sup.1] , Feng-Yee Chang[sup.1] and Leung-Kei Siu[sup.1,5,6] Background Klebsiella pneumoniae [...]

The capsular polysaccharides in different serotypes ofKlebsiella pneumoniae(KP) coded by the (CPS) gene cluster are characterized by a conserved and a hyper-variable region. We performed a virulence study by switching genes in the highly conserved region of the CPS cluster between strains. Six genes in the CPS conserved region in serotype K20, includinggalF, acidPPc, wzi, wza, wzbandwzc, were knocked out and replaced by the homologous genes from serotype K1. Compared to the parental K20 strain, the mutants showed a decline in lethality (LD50) in mice from 10-fold to > 105-fold and were categorized in terms of the effect on virulence as low (L) forgalFandacidPPC, moderate (M) forwzi, and high (H) forwza, wzbandwzc. Although substituting theacidPPCgene from K1 foracidPPCin the K20 strain fully restored virulence, substitution with thewzi, wza, wzborwzchomologs from K1 did not. The restoration withwzifrom K1 led to a partial restoration of virulence, with the LD50in mice changing from 104to 103CFU.For thewza, wzbandwzcgenes, Complementation of K20wza, wzbandwzcfrom K1 resulted in varied degrees of lethality in mice. Variable improvement in serum killing and phagocytosis was observed when the knockout mutants were compared with the gene-switched strains. In conclusion, homologous genes for capsule synthesis failed to exhibit the same functionality when switched between serotypes and virulence was decreased in different degree in according to the genes' homology. [ABSTRACT FROM AUTHOR]

Emerging risk factors for tuberculosis (TB) infection, such as air pollution, play a significant role at both the individual and population levels. However, the association between air pollution and TB remains unclear. The objective of this study was to examine the association between outdoor air pollution and sputum culture conversion in TB patients. In the present study, 389 subjects were recruited from a hospital in Taiwan from 2010 to 2012: 144 controls with non-TB-related pulmonary diseases with negative sputum cultures and 245 culture-positive TB subjects. We observed that a 1 μg/m(3) increase in particulate matter of ≤10 μm in aerodynamic diameter (PM10) resulted in 4% higher odds of TB (odds ratio =1.04, 95% confidence interval =1.01-1.08, P<0.05). The chest X-ray grading of TB subjects was correlated to 1 year levels of PM10 (R (2)=0.94, P<0.05). However, there were no associations of pulmonary cavitation or treatment success rate with PM10. In subjects with TB-positive cultures, annual exposure to ≥50 μg/m(3) PM10 was associated with an increase in the time required for sputum culture conversion (hazard ratio =1.28, 95% confidence interval: 1.07-1.84, P<0.05). In conclusion, chronic exposure to ≥50 μg/m(3) PM10 may prolong the sputum culture conversion of TB patients with sputum-positive cultures. [ABSTRACT FROM AUTHOR]

Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been associated with favorable progression free survival (PFS) in patients with non-small cell lung cancers (NSCLC) harboring EGFR mutations. However, a subset of this population doesn't respond to EGFR-TKI treatment. Therefore, the present study aimed to elucidate survival outcome in NSCLC EGFR-mutant patients who were treated with EGFR TKIs. Methods: Among the 580 consecutive NSCLC patients who were treated at our facility between 2008 and 2012, a total of 124 treatment-naïve, advanced NSCLC, EGFR-mutant patients treated with EGFR TKIs were identified and grouped into non-responders and responders for analyses. Results: Of 124 patients, 104 (84%) responded to treatment, and 20 (16%) did not; and the overall median PFS was 9.0 months. Notably, the PFS, overall survival (OS) and survival rates were significantly unfavorable in non-responders (1.8 vs. 10.3 months, hazard ratio (HR) = 29.2, 95% confidence interval (CI), 13.48–63.26, P<0.0001; 9.4 vs. 17.3 months, HR = 2.74, 95% CI, 1.52–4.94, P = 0.0008; and 58% vs. 82% in 6, 37% vs. 60% in 12, and 19 vs. 40% at 24 months, respectively). In multivariate analysis, treatment efficacy strongly affected PFS and OS, independent of covariates (HR = 47.22, 95% CI, 17.88–124.73, P<0.001 and HR = 2.74, 95% CI, 1.43–5.24, P = 0.002, respectively). However, none of the covariates except of the presence of EGFR exon 19 deletion in the tumors was significantly associated with better treatment efficacy. Conclusions: A subset of NSCLC EGFR-mutant patients displayed unfavorable survival despite EGFR TKI administration. This observation reinforces the urgent need for biomarkers effectively predicting the non-responders and for drug development overcoming primary resistance to EGFR TKIs. In addition, optimal therapeutic strategies to prolong the survival of non-responders need to be investigated. [ABSTRACT FROM AUTHOR]

Emerging risk factors for tuberculosis (TB) infection, such as air pollution, play a significant role at both the individual and population levels. However, the association between air pollution and TB remains unclear. The objective of this study was to examine the association between outdoor air pollution and sputum culture conversion in TB patients. In the present study, 389 subjects were recruited from a hospital in Taiwan from 2010 to 2012: 144 controls with non-TB-related pulmonary diseases with negative sputum cultures and 245 culture-positive TB subjects. We observed that a 1 μg/m(3) increase in particulate matter of ≤10 μm in aerodynamic diameter (PM10) resulted in 4% higher odds of TB (odds ratio =1.04, 95% confidence interval =1.01-1.08, P<0.05). The chest X-ray grading of TB subjects was correlated to 1 year levels of PM10 (R (2)=0.94, P<0.05). However, there were no associations of pulmonary cavitation or treatment success rate with PM10. In subjects with TB-positive cultures, annual exposure to ≥50 μg/m(3) PM10 was associated with an increase in the time required for sputum culture conversion (hazard ratio =1.28, 95% confidence interval: 1.07-1.84, P<0.05). In conclusion, chronic exposure to ≥50 μg/m(3) PM10 may prolong the sputum culture conversion of TB patients with sputum-positive cultures.