Fungal chitinases: diversity, mechanistic properties and biotechnological potential

Chitin derivatives, chitosan and substituted chito-oligosaccharides have a wide spectrum of applications ranging from medicine to cosmetics and dietary supplements. With advancing knowledge about the substrate-binding properties of chitinases, enzyme-based production of these biotechnologically relevant sugars from biological resources is becoming increasingly interesting. Fungi have high numbers of glycoside hydrolase family 18 chitinases with different substrate-binding site architectures. As presented in this review, the large diversity of fungal chitinases is an interesting starting point for protein engineering. In this review, recent data about the architecture of the substrate-binding clefts of fungal chitinases, in connection with their hydrolytic and transglycolytic abilities, and the development of chitinase inhibitors are summarized. Furthermore, the biological functions of chitinases, chitin and chitosan utilization by fungi, and the effects of these aspects on biotechnological applications, including protein overexpression and autolysis during industrial processes, are discussed in this review

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Extensive gross-contamination of specimens with Mycobacterium tuberculosis in a reference laboratory

A striking increase in the numbers of cultures positive for Mycobacterium tuberculosis was noticed in a mycobacterial reference laboratory in Campinas, Sao Paulo State, Brazil, in May 1995. A contaminated bronchoscope was the suspected cause of the increase. All 91 M. tuberculosis isolates grown from samples from patients between 8 May and 18 July 1995 were characterized by spoligotyping and IS6110 fingerprinting. Sixty-one of the 91 isolates had identical spoligotype patterns, and the pattern was arbitrarily designated S36. The 61 specimens containing these isolates had been processed and cultured in a 21-day period ending on 1 June 1995, but only 1 sample was smear positive for acid-fast bacilli. The patient from whom this sample was obtained was considered to be the index case patient and had a 4+ smear-positive lymph node aspirate that had been sent to the laboratory on 10 May. Virtually all organisms with spoligotype S36 had the same IS6110 fingerprint pattern. Extensive review of the patients' charts and investigation of laboratory procedures revealed that cross-contamination of specimens had occurred. Because the same strain was grown from all types of specimens, the bronchoscope was ruled out as the outbreak source. The most likely source of contamination was a multiple-use reagent used for specimen processing. The organism was cultured from two of the solutions 3 weeks after mock contamination. This investigation strongly supports the idea that M. tuberculosis grown from smear-negative specimens should be analyzed by rapid and reliable strain differentiation techniques, such as spoligotyping, to help rule out laboratory contamination.37491691