Peptides and proteins with antimicrobial activity are produced throughout all kingdoms in nature, from prokaryotes to lower and higher eukaryotes, including fungi, plants, invertebrates and ...vertebrates. These proteins contribute to an important constitutive or induced defense mechanism of the producer against microorganisms. According to their variety in structure and function, these proteins are classified arbitrarily into groups that are based on their mechanism of action, their structure and their similarity to other known proteins. The present review focuses on a new group of antimicrobial proteins, namely small, basic and cysteine-rich antifungal proteins, which are secreted from filamentous fungi of the group Ascomycetes. These proteins are encoded by orthologous genes and exhibit both similarities and differences concerning their species-specificity, primary structure, protein activity and target sites. The properties of these proteins, their possible mode of action and their potential application for human benefits are discussed in comparison with other already well known antimicrobial proteins.
ALTHOUGH CURABLE, TB frequently leaves the individual with chronic physical and psycho-social impairment, but these consequences have been largely neglected. The 1
International Post-Tuberculosis ...Symposium (Stellenbosch, South Africa) was held to discuss priorities and gaps in addressing this issue. A barrier to progress has been the varied terminology and nomenclature, so the Delphi process was used to achieve consensus on definitions. Lack of sufficient evidence hampered definitive recommendations in most domains, including prevention and treatment of post-TB lung disease (PTLD), but the discussions clarified the research needed. A consensus was reached on a toolkit for future PTLD measurement and on PTLD patterns to be considered. The importance of extra-pulmonary consequences and progressive impairment throughout the life-course was identified, including TB recurrence and increased mortality. Patient advocates emphasised the need to address the psychological and social impacts post TB and called for clinical guidance. More generally, there is an urgent need for increased awareness and research into post-TB complications.
Recurrent tuberculosis (TB), defined as TB that recurs after a patient has been considered cured, constitutes a challenge to TB control. In low TB burden countries, the underlying causes and ...consequences of recurrent TB are poorly understood. We conducted a literature review to summarise the evidence of recurrent TB in low-burden settings and to address current gaps in knowledge. We included peer-reviewed publications on studies conducted in countries with an estimated TB incidence of <100 cases per 100 000 population. The Newcastle-Ottawa scale was used to assess study quality. The review yielded 44 manuscripts, 39 of which were reports of observational studies and 5 of clinical trials. The median percentage of TB patients experiencing an episode of recurrent TB after treatment completion was 3.4% (interquartile range IQR 1.6-6.0, range 0.4-16.7) in studies with a median follow-up of 7.8 years (IQR 5-12, range 2-33). The median percentage of recurrences attributable to endogenous reactivation (rather than exogenous reinfection) was 81% (IQR 73.1-85.5, range 49-100). Commonly identified risk factors for recurrence in low-burden settings included infection by the human immunodeficiency virus, low socio-economic status, foreign birth and infection with drug-resistant TB. Current understanding of recurrence in low-burden settings is limited, in part due to substantial methodological differences between studies. Further research is required to delineate the mechanisms of TB recurrence, its health and clinical impact, as well as the implications for TB elimination efforts in low-burden countries.
The filamentous fungus Penicillium chrysogenum Q176 secretes the antimicrobial proteins (AMPs) PAF and PAFB, which share a compact disulfide-bond mediated, β-fold structure rendering them highly ...stable. These two AMPs effectively inhibit the growth of human pathogenic fungi in micromolar concentrations and exhibit antiviral potential without causing cytotoxic effects on mammalian cells in vitro and in vivo.
The antifungal mechanism of action of both AMPs is closely linked to - but not solely dependent on - the lipid composition of the fungal cell membrane and requires a strictly regulated protein uptake into the cell, indicating that PAF and PAFB are not canonical membrane active proteins. Variations in their antifungal spectrum and their killing dynamics point towards a divergent mode of action related to their physicochemical properties and surface charge distribution.
In this review, we relate characteristic features of PAF and PAFB to the current knowledge about other AMPs of different sources. In addition, we present original data that have never been published before to substantiate our assumptions and provide evidences that help to explain and understand better the mechanistic function of PAF and PAFB. Finally, we underline the promising potential of PAF and PAFB as future antifungal therapeutics.
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•Penicillium chrysogenum secretes the small, cysteine-rich proteins PAF and PAFB.•Both exhibit antifungal activity, but with differences in their mode of action.•Structure, membrane interaction and cellular uptake determine their function.•PAF and PAFB are well tolerated by mammalian cells.•They promise applicability in medicine, plant protection and food industry.
Background Substantial additional efforts are needed to prevent, find and successfully treat tuberculosis (TB) in South Africa (SA). In the past decade, an increasing body of mathematical modelling ...research has investigated the population-level impact of TB prevention and care interventions. To date, this evidence has not been assessed in the SA context.Objective To systematically review mathematical modelling studies that estimated the impact of interventions towards the World Health Organization’s End TB Strategy targets for TB incidence, TB deaths and catastrophic costs due to TB in SA.Methods We searched the PubMed, Web of Science and Scopus databases for studies that used transmission-dynamic models of TB in SA and reported on at least one of the End TB Strategy targets at population level. We described study populations, type of interventions and their target groups, and estimates of impact and other key findings. For studies of country-level interventions, we estimated average annual percentage declines (AAPDs) in TB incidence and mortality attributable to the intervention.Results We identified 29 studies that met our inclusion criteria, of which 7 modelled TB preventive interventions (vaccination, antiretroviral treatment (ART) for HIV, TB preventive treatment (TPT)), 12 considered interventions along the care cascade for TB (screening/case finding, reducing initial loss to follow-up, diagnostic and treatment interventions), and 10 modelled combinations of preventive and care-cascade interventions. Only one study focused on reducing catastrophic costs due to TB. The highest impact of a single intervention was estimated in studies of TB vaccination, TPT among people living with HIV, and scale-up of ART. For preventive interventions, AAPDs for TB incidence varied between 0.06% and 7.07%, and for care-cascade interventions between 0.05% and 3.27%.Conclusion We describe a body of mathematical modelling research with a focus on TB prevention and care in SA. We found higher estimates of impact reported in studies of preventive interventions, highlighting the need to invest in TB prevention in SA. However, study heterogeneity and inconsistent baseline scenarios limit the ability to compare impact estimates between studies. Combinations, rather than single interventions, are likely needed to reach the End TB Strategy targets in SA.
Based on mapping of laterally traceable stratigraphic discontinuities, we propose a high-resolution allostratigraphic scheme for one of the world's foremost fossil marine vertebrate Lagerstätten: the ...lower Miocene strata of the Chilcatay Formation exposed along the Ica River near Zamaca, southern Peru. Measured sections combined with 1:10,000 scale mapping of a 24 km
2
area provide an overview of the stratal architecture, as well as a general facies framework and interpretation of the various depositional settings. As a whole, the Chilcatay alloformation is bounded by the CE0.1 unconformity at the base and the PE0.0 unconformity at the top. An internal Chilcatay surface, termed CE0.2, splits the alloformation into two distinct allomembers (Ct1 and Ct2). The Ct1 allomember comprises three facies associations recording deposition in shoreface, offshore, and subaqueous delta settings. The Ct2 allomember comprises two facies associations, recording deposition in shoreface and offshore settings. Using these data, we place the rich marine vertebrate assemblage in a precise spatial and stratigraphic framework. The well-diversified vertebrate assemblage is dominated by cetaceans (mostly odontocetes) and sharks (mostly lamniforms and carcharhiniforms); rays, bony fish, and turtles are also present. Taxonomic novelties include the first records of baleen whales, platanistids, and eurhinodelphinids from the Chilcatay Formation.
In recent years the interest in antimicrobial proteins and peptides and their mode of action has been rapidly increasing due to their potential to prevent and combat microbial infections in all areas ...of life. A detailed knowledge about the function of such proteins is the most important requirement to consider them for future application. Our research in recent years has been focused on the low molecular weight, cysteine-rich and cationic antifungal protein PAF from Penicillium chrysogenum, which inhibits the growth of opportunistic zoo-pathogens including Aspergillus fumigatus, numerous plant-pathogenic fungi and the model organism Aspergillus nidulans. So far, the experimental results indicate that PAF elicits hyperpolarization of the plasma membrane and the activation of ion channels, followed by an increase in reactive oxygen species in the cell and the induction of an apoptosis-like phenotype. Detailed knowledge about the molecular mechanism of action of antifungal proteins such as PAF contributes to the development of new antimicrobial strategies that are urgently needed.
Persistent respiratory symptoms and lung function deficits are common after patients with TB. We aimed to define the burden of post-TB lung disease (PTLD) and assess associations between symptoms and ...impairment in two high TB incidence communities.
This was a cross-sectional survey of adults in Cape Town, South Africa who completed TB treatment 1-5 years previously. Questionnaires, spirometry and 6-minute walking distance (6MWD) were used to assess relationships between outcome measures and associated factors.
Of the 145 participants recruited (mean age: 42 years, range: 18-75; 55 38% women), 55 (38%) had airflow obstruction and 84 (58%) had low forced vital capacity (FVC); the mean 6MWD was 463 m (range: 240-723). Respiratory symptoms were common: chronic cough (
= 27, 19%), wheeze (
= 61, 42%) and dyspnoea (modified MRC dyspnoea score 3 or 4:
= 36, 25%). There was poor correlation between FVC or obstruction and 6MWD. Only low body mass index showed consistent association with outcomes on multivariable analyses. Only 19 (13%) participants had a diagnosis of respiratory disease, and 16 (11%) currently received inhalers.
There was substantial burden of symptoms and physiological impairment in this "cured" population, but poor correlation between objective outcome measures, highlighting deficits in our understanding of PTLD.
Background The Association for Professionals in Infection Control and Epidemiology (APIC) MegaSurvey, administered in 2015, was completed by approximately 4,079 APIC members. The survey sought to ...gain a better understanding the current state of 4 components of infection prevention practice: demographic characteristics, compensation, organizational structure, and practice and competency. Methods The data for this analysis come from the APIC MegaSurvey Practice and Competency domain. Descriptive statistics and χ2 analyses were conducted to examine differences in infection preventionist (IP) competency, roles, and activity self-assessments. Results The majority of IPs self-assessed their competency as Proficient compared with Novice or Expert for each of the 8 IP core competency activities. Forty percent of IPs self-rated their competency as Expert in the Preventing/Controlling the Transmission of Infectious Agents/HAIs component. IPs reported Novice competency in Employee/Occupational Health (29%); Cleaning, Sterilization, Disinfection, and Asepsis (23%); and Education and Research categories (22%). Differences in self-rated competency among IPs by discipline type (public health, nurse, and laboratory) were identified. Conclusions Differences in self-rated competency were identified for each of the 8 IP core competency activities. IPs report using various resource types to gain competency. Future research is needed to identify opportunities to increase competency levels in the weakest-rated competency activities.
To investigate the uptake and usage of a WhatsApp-based interactive communication strategy to avert pre-diagnosis loss to follow-up (LTFU) from TB care in a high-incidence setting.
We enrolled adults ...(≥18 years) who underwent routine sputum TB testing in two primary healthcare clinics in Khayelitsha, Cape Town, South Africa. The intervention consisted of structured WhatsApp-based reminders (prompts) sent prior to a routine clinic appointment scheduled 2-3 days after the diagnostic visit. Pre-diagnosis LTFU was defined as failure to return for the scheduled appointment and within 10 days.
We approached 332 adults with presumptive TB, of whom 103 (31%) were successfully enrolled; 213 (64%) did not own a WhatsApp-compatible phone. Of 103 participants, 74 (72%) actively responded to WhatsApp prompts; 69 (67%) opted to include a close contact in group communication to co-receive reminders. Pre-diagnosis LTFU was low overall (
= 7, 6.8%) and was not associated with failure to respond to WhatsApp prompts.
In this high-incidence setting, enrolment in a WhatsApp-based communication intervention among adults with presumptive TB was low, mainly due to low availability of WhatsApp-compatible phones. Among participants, we observed high message response rates and low LTFU, suggesting potential for interactive messaging services to support pre-diagnosis TB care.
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