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The Sec61/SecY channel allows the translocation of many proteins across the eukaryotic endoplasmic reticulum membrane or the prokaryotic plasma membrane. In bacteria, most secretory proteins are transported post-translationally through the SecY channel by the SecA ATPase. How a polypeptide is moved through the SecA-SecY complex is poorly understood, as structural information is lacking. Here, we report an electron cryo-microscopy (cryo-EM) structure of a translocating SecA-SecY complex in a lipid environment. The translocating polypeptide chain can be traced through both SecA and SecY. In the captured transition state of ATP hydrolysis, SecAs two-helix finger is close to the polypeptide, while SecAs clamp interacts with the polypeptide in a sequence-independent manner by inducing a short β-strand. Taking into account previous biochemical and biophysical data, our structure is consistent with a model in which the two-helix finger and clamp cooperate during the ATPase cycle to move a polypeptide through the channel.

A 73-year-old male presented with erythema and papules all over the body with itching for 2 months, aggravated for 1 week. Eight months ago, he received immunotherapy with programmed cell death receptor 1 (PD-1) inhibitor for colorectal cancer, and 2 months ago, erythema and papules all over the body appeared, accompanied by severe itching. Dermatologic examination showed flaky erythema on the trunk and extremities, partially fused into a large area with scattered erythematous papules, scratches, and hyperpigmentation. Histopathology showed epidermal parakeratosis, hypertrophy of the stratum spinosum, and mild localized interspinous cell edema; capillary dilatation in the superficial dermis, predominantly peritubular lymphocytes, and occasional eosinophils. Diagnosis: immune checkpoint inhibitor-related skin toxicity (maculopapular rash with pruritus). After multidisciplinary discussion and informed consent, the patient was initiated on dupilumab therapy, administered as a 600 mg subcutaneous injection, followed by 300 mg doses every two weeks for a total of three treatments. The skin lesions and itching improved, and the patient was still under follow-up. % [ABSTRACT FROM AUTHOR]

Objective: Antibiotics have been routinely used for several decades against Propionibacterium acnes ( P. acnes ), but antibiotic resistance of P. acnes is becoming a global problem. Only one related Chinese study is available. The aim of this study was to assess the antibiotic susceptibility of P. acnes obtained from patients with acne in Southwest China., Design: This was a prospective cross-sectional study. Cutaneous samples were obtained from acne lesions on the face of 375 patients. Samples were cultured in anaerobic medium to identify the presence of P. acnes . Susceptibility tests of isolated P. acnes were performed for tetracycline, doxycycline, clindamycin, erythromycin, azithromycin and clarithromycin using the Epsilometer test., Results: P. acnes was isolated from 227 patients; 224 isolates (98.7%) were susceptible to doxycycline and 220 (96.9%) were susceptible to tetracycline, followed by clindamycin and clarithromycin in 101 (44.5%) and 102 (44.93%) isolates, respectively. Susceptibility of P. acnes was detected for erythromycin in 96 (42.3%) patients, followed by azithromycin in 94 (41.4%). Subjects who received antibiotics (topical and oral) had higher frequencies of antibiotic-resistant P. acnes as well as increased antibiotic minimum inhibitory concentrations compared with patients without antibiotic treatment., Conclusions: P. acnes was highly sensitive to cyclines (doxycycline and tetracycline). P. acnes showed higher resistance rates to macrolides-lincosamides-streptogramins antibiotics (such as erythromycin, azithromycin, clarithromycin and clindamycin). The irrational use of antibiotics for acne treatment is probably a problem in China and elsewhere. These results suggest that dermatologists should be more prudent in prescribing antibiotics for acne., Competing Interests: Competing interests: Not required., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)