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Pseudomonas syringae pv. tomato, the causal agent of bacterial speck of tomato, has recently become an increasing problem in California due to the evolution and prevalence of highly aggressive race 1 strains. In resistant plant genotypes, the type III effectors AvrPto and AvrPtoB are recognized by the tomato proteins Pto and Prf. We investigated the prevalence of avrPto and avrPtoB in strains collected over the last 13 years in California. All race 1 strains retained avrPtoB but did not express AvrPtoB protein at detectable levels in vitro. However, deletion of avrPtoB indicated that this effector protein is still expressed at low levels in race 1 during infection. avrPto was detected in four race 1 strains but a key amino acid polymorphism prevents this new protein from interacting with and eliciting Pto-mediated resistance. Growth curve analyses demonstrate that this new avrPto allele is still functional and can enhance P. syringae virulence on tomato. Multilocus sequence typing was used to resolve phylogenetic relationships and revealed that the majority of race 0 and 1 strains were most closely related to P. syringae T1. Collectively, these data support the hypothesis that existing P. syringae populations evolved to overcome genetic resistance by altering the expression and sequence of avrPto and avrPtoB effectors.

Objectives: To assess the steady-state pharmacokinetics of two reduced doses of indinavir boosted with ritonavir (indinavir/ritonavir) in HIV-infected Thai patients.Patients and methods: Thirteen immunocompromised antiretroviral-naive patients (6 males, 7 females) initiated 600/100 mg indinavir/ritonavir, zidovudine and lamivudine, every 12 h. After 1 month, blood samples were taken at pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 h after drug intake. Indinavir dosing was then reduced to 400 mg (twice daily) and 1 week later an identical series of samples were drawn. Patients then resumed 600 mg of indinavir. HIV-1 RNA viral load was determined at 8, 24 and 48 weeks. Indinavir plasma levels were determined by HPLC and pharmacokinetic parameters by non-compartmental analysis.Results: Median (range) weight was 58 kg (51–73) for men and 53 kg (46–59) for women. On 600 mg of indinavir, median indinavir AUC, Cmax, and Cmin were 39.3 mg·h/L (20.6–50.5), 6.2 mg/L (3.7–9.0) and 0.41 mg/L (0.12–0.77), respectively, and on indinavir 400 mg, 18.3 mg·h/L (11.1–33.0), 3.8 mg/L (2.2–7.8) and 0.17 mg/L (0.10–0.39), respectively. No renal complications were observed. At 48 weeks, 6/13 (46%) patients had stopped 600 mg of indinavir due to intolerability (gastrointestinal and cutaneous), and 5/7 (71%) patients had a HIV-1 viral load <50 copies/mL.Conclusions: Reduced doses of indinavir/ritonavir maintained adequate indinavir plasma levels compared to current guidelines suggesting that these doses are efficacious in this setting. Considering the poor tolerability of 600 mg of indinavir, the 400 mg of indinavir may be preferred due to its lower exposure indices but long-term efficacy data are needed. [ABSTRACT FROM AUTHOR]