Ceftazidime-Avibactam Treatment for Klebsiella pneumoniae Bacteremia in Preterm Infants in NICU: A Clinical Experience.

Ceftazidime/avibactam (CAZ/AVI) is an antibiotic combination approved for the treatment of several infections caused by multi-drug resistant (MDR) Gram-negative bacteria. Neonates admitted to the Neonatal Intensive Care Unit (NICU) are at high risk of developing bacterial infections, and the choice of appropriate antibiotics is crucial. However, the use of antibiotics in neonates carries risks such as antibiotic resistance and disruption of gut microbiota. This study aimed to assess the safety and efficacy of CAZ/AVI in preterm infants admitted to the NICU. Retrospective data from preterm infants with Klebsiella pneumoniae bacteremia who received CAZ/AVI were analyzed. Clinical and microbiological responses, adverse events, and outcomes were evaluated. Eight patients were included in the study, all of whom showed clinical improvement and achieved microbiological cure with CAZ/AVI treatment. No adverse drug reactions were reported. Previous antibiotic therapies failed to improve the neonates' condition, and CAZ/AVI was initiated based on clinical deterioration and epidemiological considerations. The median duration of CAZ/AVI treatment was 14 days, and combination therapy with fosfomycin or amikacin was administered. Previous case reports have also shown positive outcomes with CAZ/AVI in neonates. However, larger trials are needed to further investigate the safety and efficacy of CAZ/AVI in this population.

Diagnosis, Treatment, and Prevention of HIV Infection among Detainees: A Review of the Literature.

Detainees are one of the most vulnerable populations to human immunodeficiency virus (HIV). This is mostly caused by the lack of knowledge on the topic among the inmates; the lack of prophylaxis; the high percentage of risky behaviors in jail, such as sexual abuse, unprotected sexual intercourses, and injective drug use; and the generally low perception of the risk of transmission. It has also been observed that the problem does not cease to exist at the moment of release, but it also may be aggravated by the weak support system or the total absence of programs for people living with HIV/AIDS (PLWHA) to avoid discontinuation of antiretroviral drugs. Difficulty in providing housing and jobs and, therefore, a form of stability for ex-detainees, also contributes to none adherence to antiretroviral therapy. Among the detainees, there are also categories of people more susceptible to discrimination and violence and, therefore, to risky behaviors, such as black people, Hispanics, transgender people, and men who have sex with men (MSM). We reviewed the literature in order to provide a more complete picture on the situation of PLWHA in jail and to also analyze the difficulties of ex-detainees in adhering to HIV therapy.

Efficacy of COVID-19 Vaccination in People Living with HIV: A Public Health Fundamental Tool for the Protection of Patients and the Correct Management of Infection.

HIV/AIDS is considered a risk factor for increased mortality due to COVID-19. For this reason, it is essential to include this population in vaccination campaigns. Studies found that antibodies are lower in HIV+ patients than in healthy individuals. The aim of this study was to assess the immune response in a cohort of people living with HIV/AIDS (PLWH) vaccinated with COVID-19 vaccination in order to evaluate the role played by the HIV infection in the efficacy of this vaccine. We carried out a cross-sectional study in the period April-September 2021, involving a cohort of PLWH and a cohort of HIV-uninfected people as the control group. The efficacy of vaccination was high in both groups despite a slight and not significant difference between them. However, important differences were found according to the intensity of the immune response. Specifically, while in the HIV+ group almost a quarter of people had a low response, it is important to remark that the control group had only a high or intermediate response after vaccination. Our results suggest the high efficacy of the mRNA COVID-19 vaccine in PLWH and the importance to vaccinate against COVID-19 in these patients in order to increase their protection.

Thyroid Diseases and Thyroid Asymptomatic Dysfunction in People Living With HIV.

Thyroid diseases (TDs) and thyroid asymptomatic dysfunctions (TADs) are correlated with Human Immunodeficiency virus (HIV) infection and Acquired ImmunoDeficiency Syndrome (AIDS) as well as many endocrine dysfunctions and dysregulation of hormonal axes. To date, available studies on People Living With HIV (PLWH) affected by thyroid diseases and asymptomatic dysfunctions are few and rather controversial. The purpose of the present non-systematic literature review is to recap the current knowledge on the main features of thyroid dysfunctions and disorders in PLWH. Large cohort studies are needed for a better comprehension of the impact, evolution and treatment of thyroid pathologies in the HIV-infected population.

HIV and Mediterranean Zoonoses: A Review of the Literature.

A zoonosis is an infectious disease that has jumped from a non-human animal to humans. Some zoonoses are very common in the Mediterranean area and endemic in specific regions, so they represent an important problem for public health. Human Immunodeficiency Virus (HIV) is a virus that has originated as a zoonosis and is now diffused globally, with the most significant numbers of infected people among the infectious diseases. Since the introduction of antiretroviral therapy (ART), the history for people living with HIV (PLWH) has changed drastically, and many diseases are now no different in epidemiology and prognosis as they are in not-HIV-infected people. Still, the underlying inflammatory state that is correlated with HIV and other alterations related to the infection itself can be a risk factor when infected with other bacteria, parasites or viruses. We reviewed the literature for infection by the most common Mediterranean zoonoses, such as Campylobacter, Salmonella, Brucella, Rickettsia, Borrelia, Listeria and Echinococcus, and a possible correlation with HIV. We included Monkeypox, since the outbreak of cases is becoming a concern lately. We found that HIV may be related with alterations of the microbiome, as for campylobacteriosis, and that there are some zoonoses with a significant prevalence in PLWH, as for salmonellosis.

Arteriovenous fistula thrombosis in hemodialysis patients with COVID-19: epiphenomenon or marker of severe clinical disease?

Background: Pandemic condition due to Coronavirus disease (COVID-19) caused a fastest augmentation of hospitalization, impairing the healthcare organization. As a consequence, diagnostic and therapeutic delays have been showed. COVID-19-associated coagulopathy is an endothelial disease related to SARSCoV-2 infection. Our study evaluated the thrombosis of arteriovenous fistula (AVF) as risk marker of mortality. Methods: the analysis included 24 dialysis-dependent patients admitted in a period between March 2020 and June 2021. Patients were divided based on AVF thrombosis: the A group without AVF thrombosis (13 patients), and the B group with AVF thrombosis events (11 patients). Pearson or Spearman' correlation tests were performed to detect possible confounding variable to include in multivariate models. Kaplan Meier and Cox regression analysis were performed to compute mortality analysis. Results: Delta D-dimer (Rho: 0.613, p=0.007), over-infections (Rho 0.456; p= 0,026), C-reactive Protein (CRP) (Rho=0.417, p=0.043), death (Rho=0.492, p=0.027), positive pulmonary imaging (Rho 0.388, p=0.074), and high OLT (0.408, p=0.047) were related to AVF thrombosis, using Pearson or Spearman correlation tests. Kaplan Meier test showed a death average of 19 days in group B compared to a global average of 38 days (p=0.029), and Cox analysis showed an HR of 5.01, 95% CI 1.01-24.99, p=0.049. Furthermore, AVF thrombosis explained about the 68% of the mortality, evaluated through the Harrel's C test. Conclusion: We can speculate that AVF thrombosis in hemodialysis patients with COVID-19 could be an early marker of both pro-coagulative process and severe clinical disease and it could be used to stratify patients and identify the ones that can be considered "frail".

Pulmonary Kaposi Sarcoma without Respiratory Symptoms and Skin Lesions in an HIV-Naïve Patient: A Case Report and Literature Review.

Kaposi sarcoma (KS) is a multifocal lympho-angioproliferative, mesenchymal low-grade tumor associated with a γ2-herpesvirus, named Kaposi sarcoma-associated virus or human herpesvirus (KSHV/HHV8). The lung is considered a usual anatomical location of KS, despite being infrequent, often in association with extensive mucocutaneous lesions and very uncommonly as an isolated event. We report a case of a pulmonary KS (pKS) in a human immunodeficiency virus (HIV) naïve patient, which was atypical due to a lack of cutaneous involvement and an absence of respiratory symptoms. The pKS was initially identified as a tumoral suspected nodular lesion and only after immunohistochemical analysis was it characterized as KS. Furthermore, the diagnosis of pKS led to the discovery of the HIV-seropositive status of the patient, previously unknown. Our report underlines the importance of considering pKS even without skin lesions and as a first manifestation of HIV infection. We also reviewed literature on the current knowledge about pKS in people living with HIV (PLWH) to underline how one of the most common HIV/acquired immunodeficiency syndrome (AIDS) associated tumors can have a challenging localization and be difficult to recognize.

Loco-Regional Treatments for Hepatocellular Carcinoma in People Living with HIV.

Hepatocellular carcinoma (HCC) accounts for approximately 75-90% of primary liver cancers and is the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. In the HIV-positive population, the risk of HCC is approximately four times higher than in the general population, with higher cancer-specific mortality than in HIV-negative patients. In most cases, HCC diagnosis is made in patients younger than the HIV-negative population and in the intermediate-advanced stage, thus limiting the therapeutic possibilities. Treatment choice in HIV-positive patients with HCC is subject to cancer staging, liver function and health status, as for HIV-negative and non-HIV-negative HCC patients. There are relatively few studies on the efficacy and safety in HIV-positive patients to date in loco-regional treatments for HCC. So far, literature shows that curative treatments such as radiofrequency ablation (RFA) have no significant differences in overall survival between HIV-positive and HIV-negative patients, as opposed to palliative treatments such as TACE, where there is a significant difference in overall survival. Although it can be assumed that the most recently discovered loco-regional therapies are applicable to HIV-positive patients with HCC in the same way as HIV-negative patients, further studies are needed to confirm this hypothesis. The purpose of our review is to evaluate these treatments, their efficacy, effectiveness, safety and their applicability to HIV-positive patients.

Favourable course in a cohort of Parkinson's disease patients infected by SARS-CoV-2: a single-centre experience.

The COVID-19 outbreak has had a dramatic impact on the healthcare system due to the rapid, worldwide spread of the virus, highlighting several considerations on the best management of infected patients and also potential risks and prognostic factors in patients with pre-existing chronic diseases exposed to the virus. Neurodegenerative disorders are known to be chronic, disabling diseases that imply a higher vulnerability to infections, and for this reason, it has been suggested that SARS-CoV-2 infection may have a worse course in these patients. In the present study, we report our experience with 12 patients affected by Parkinson's disease (PD) who became infected with SARS-Cov-2 due to a COVID-19 outbreak in a care residency, and thus hospitalised in our COVID hospital. Most of the PD patients had a long disease duration and multiple comorbidities even though SARS-CoV-2 manifestations were mild, and none required intensive care. Despite lung conditions, most of our PD patients had mild symptoms: 7 patients were clinically asymptomatic (58.3%); 3 patients had fever, cough, and myalgia (25%) and 2 patients had dyspnoea (16%) that needed high-flow oxygen therapy. Few complications related to PD were seen. All patients were discharged after a mean hospitalisation period of 30 days. Mortality rate during hospitalisation was zero. Our findings suggest that SARS-CoV-2 infection does not have a poor prognosis in patients with PD. More extensive data and evaluations, however, are needed to confirm our data, and caution is warranted.

Malignant melanoma in HIV: Epidemiology, pathogenesis, and management.

People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV-infected people is 2.6-fold higher than in uninfected ones. In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV-negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV-positive patients regardless of their CD4+ count and the use of standard surgical margins for re-excision procedures. In case of diagnosis of melanoma in HIV-positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV-positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow-up, every 3 months, for the first 2 years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint-based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV.

Key Components of Different Plant Defense Pathways Are Dispensable for Powdery Mildew Resistance of the Arabidopsis mlo2 mlo6 mlo12 Triple Mutant.

Loss of function mutations of particular plant MILDEW RESISTANCE LOCUS O (MLO) genes confer durable and broad-spectrum penetration resistance against powdery mildew fungi. Here, we combined genetic, transcriptomic and metabolomic analyses to explore the defense mechanisms in the fully resistant Arabidopsis thaliana mlo2 mlo6 mlo12 triple mutant. We found that this genotype unexpectedly overcomes the requirement for indolic antimicrobials and defense-related secretion, which are critical for incomplete resistance of mlo2 single mutants. Comparative microarray-based transcriptome analysis of mlo2 mlo6 mlo12 mutants and wild type plants upon Golovinomyces orontii inoculation revealed an increased and accelerated accumulation of many defense-related transcripts. Despite the biotrophic nature of the interaction, this included the non-canonical activation of a jasmonic acid/ethylene-dependent transcriptional program. In contrast to a non-adapted powdery mildew pathogen, the adapted powdery mildew fungus is able to defeat the accumulation of defense-relevant indolic metabolites in a MLO protein-dependent manner. We suggest that a broad and fast activation of immune responses in mlo2 mlo6 mlo12 plants can compensate for the lack of single or few defense pathways. In addition, our results point to a role of Arabidopsis MLO2, MLO6, and MLO12 in enabling defense suppression during invasion by adapted powdery mildew fungi.

Interaction of a Blumeria graminis f. sp. hordei effector candidate with a barley ARF-GAP suggests that host vesicle trafficking is a fungal pathogenicity target.

Filamentous phytopathogens, such as fungi and oomycetes, secrete effector proteins to establish successful interactions with their plant hosts. In contrast with oomycetes, little is known about effector functions in true fungi. We used a bioinformatics pipeline to identify Blumeria effector candidates (BECs) from the obligate biotrophic barley powdery mildew pathogen, Blumeria graminis f. sp. hordei (Bgh). BEC1-BEC5 are expressed at different time points during barley infection. BEC1, BEC2 and BEC4 have orthologues in the Arabidopsis thaliana-infecting powdery mildew fungus Golovinomyces orontii. Arabidopsis lines stably expressing the G. orontii BEC2 orthologue, GoEC2, are more susceptible to infection with the non-adapted fungus Erysiphe pisi, suggesting that GoEC2 contributes to powdery mildew virulence. For BEC3 and BEC4, we identified thiopurine methyltransferase, a ubiquitin-conjugating enzyme, and an ADP ribosylation factor-GTPase-activating protein (ARF-GAP) as potential host targets. Arabidopsis knockout lines of the respective HvARF-GAP orthologue (AtAGD5) allowed higher entry levels of E. pisi, but exhibited elevated resistance to the oomycete Hyaloperonospora arabidopsidis. We hypothesize that ARF-GAP proteins are conserved targets of powdery and downy mildew effectors, and we speculate that BEC4 might interfere with defence-associated host vesicle trafficking.

Transcriptome analysis of enriched Golovinomyces orontii haustoria by deep 454 pyrosequencing.

Powdery mildews are phytopathogenic ascomycetes that have an obligate biotrophic lifestyle and establish intimate relationships with their plant hosts. A crucial aspect of this plant-fungus interaction is the formation of specialized fungal infection structures termed haustoria. Although located within the cell boundaries of plant epidermal cells, haustoria remain separated from the plant cytoplasm by a host plasma membrane derivative, the extrahaustorial membrane. Haustoria are thought to represent pivotal sites of nutrient uptake and effector protein delivery. We enriched haustorial complexes from Arabidopsis thaliana plants infected with the powdery mildew fungus Golovinomyces orontii and performed in-depth transcriptome analysis by 454-based pyrosequencing of haustorial cDNAs. We assembled 7077 expressed sequence tag (EST) contigs with greater than 5-fold average coverage and analyzed these with regard to the respective predicted protein functions. We found that transcripts coding for gene products with roles in protein turnover, detoxification of reactive oxygen species and fungal pathogenesis are abundant in the haustorial EST contigs, while surprisingly transcripts encoding presumptive nutrient transporters were not highly represented in the haustorial cDNA library. A substantial proportion (∼38%) of transcripts coding for predicted secreted proteins comprises effector candidates. Our data provide valuable insights into the transcriptome of the key infection structure of a model obligate biotrophic phytopathogen.

Biogenesis of a specialized plant-fungal interface during host cell internalization of Golovinomyces orontii haustoria.

Powdery mildew fungi are biotrophic pathogens that require living plant cells for their growth and reproduction. Elaboration of a specialized cell called a haustorium is essential for their pathogenesis, providing a portal into host cells for nutrient uptake and delivery of virulence effectors. Haustoria are enveloped by a modified plant plasma membrane, the extrahaustorial membrane (EHM), and an extrahaustorial matrix (EHMx), across which molecular exchange must occur, but the origin and composition of this interfacial zone remains obscure. Here we present a method for isolating Golovinomyces orontii haustoria from Arabidopsis leaves and an ultrastructural characterization of the haustorial interface. Haustoria were progressively encased by deposits of plant cell wall polymers, delivered by secretory vesicles and multivesicular bodies (MVBs) that ultimately become entrapped within the encasement. The EHM and EHMx were not labelled by antibodies recognizing eight plant cell wall and plasma membrane antigens. However, plant resistance protein RPW8.2 was specifically recruited to the EHMs of mature haustoria. Fungal cell wall-associated molecular patterns such as chitin and ß-1,3-glucans were exposed at the surface of haustoria. Fungal MVBs were abundant in haustoria and putative exosome vesicles were detected in the paramural space and EHMx, suggesting the existence of an exosome-mediated secretion pathway.

Genome expansion and gene loss in powdery mildew fungi reveal tradeoffs in extreme parasitism.

Powdery mildews are phytopathogens whose growth and reproduction are entirely dependent on living plant cells. The molecular basis of this life-style, obligate biotrophy, remains unknown. We present the genome analysis of barley powdery mildew, Blumeria graminis f.sp. hordei (Blumeria), as well as a comparison with the analysis of two powdery mildews pathogenic on dicotyledonous plants. These genomes display massive retrotransposon proliferation, genome-size expansion, and gene losses. The missing genes encode enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, probably reflecting their redundancy in an exclusively biotrophic life-style. Among the 248 candidate effectors of pathogenesis identified in the Blumeria genome, very few (less than 10) define a core set conserved in all three mildews, suggesting that most effectors represent species-specific adaptations.

Coevolution between a family of parasite virulence effectors and a class of LINE-1 retrotransposons.

Parasites are able to evolve rapidly and overcome host defense mechanisms, but the molecular basis of this adaptation is poorly understood. Powdery mildew fungi (Erysiphales, Ascomycota) are obligate biotrophic parasites infecting nearly 10,000 plant genera. They obtain their nutrients from host plants through specialized feeding structures known as haustoria. We previously identified the AVR(k1) powdery mildew-specific gene family encoding effectors that contribute to the successful establishment of haustoria. Here, we report the extensive proliferation of the AVR(k1) gene family throughout the genome of B. graminis, with sequences diverging in formae speciales adapted to infect different hosts. Also, importantly, we have discovered that the effectors have coevolved with a particular family of LINE-1 retrotransposons, named TE1a. The coevolution of these two entities indicates a mutual benefit to the association, which could ultimately contribute to parasite adaptation and success. We propose that the association would benefit 1) the powdery mildew fungus, by providing a mechanism for amplifying and diversifying effectors and 2) the associated retrotransposons, by providing a basis for their maintenance through selection in the fungal genome.

Extracellular transport and integration of plant secretory proteins into pathogen-induced cell wall compartments.

Many fungal parasites enter plant cells by penetrating the host cell wall and, thereafter, differentiate specialized intracellular feeding structures, called haustoria, by invagination of the plant's plasma membrane. Arabidopsis PEN gene products are known to act at the cell periphery and function in the execution of apoplastic immune responses to limit fungal entry. This response underneath fungal contact sites is tightly linked with the deposition of plant cell wall polymers, including PMR4/GSL5-dependent callose, in the paramural space, thereby producing localized wall thickenings called papillae. We show that powdery mildew fungi specifically induce the extracellular transport and entrapment of the fusion protein GFP-PEN1 syntaxin and its interacting partner monomeric yellow fluorescent protein (mYFP)-SNAP33 within the papillary matrix. Remarkably, PMR4/GSL5 callose, GFP-PEN1, mYFP-SNAP33, and the ABC transporter GFP-PEN3 are selectively incorporated into extracellular encasements surrounding haustoria of the powdery mildew Golovinomyces orontii, suggesting that the same secretory defense responses become activated during the formation of papillae and haustorial encasements. This is consistent with a time-course analysis of the encasement process, indicating that these extracellular structures are generated through the extension of papillae. We show that PMR4/GSL5 callose accumulation in papillae and haustorial encasements occurs independently of PEN1 syntaxin. We propose a model in which exosome biogenesis/release serves as a common transport mechanism by which the proteins PEN1 and PEN3, otherwise resident in the plasma membrane, together with membrane lipids, become stably incorporated into both pathogen-induced cell wall compartments.

The Powdery Mildew Disease of Arabidopsis: A Paradigm for the Interaction between Plants and Biotrophic Fungi.

The powdery mildew diseases, caused by fungal species of the Erysiphales, have an important economic impact on a variety of plant species and have driven basic and applied research efforts in the field of phytopathology for many years. Although the first taxonomic reports on the Erysiphales date back to the 1850's, advances into the molecular biology of these fungal species have been hampered by their obligate biotrophic nature and difficulties associated with their cultivation and genetic manipulation in the laboratory. The discovery in the 1990's of a few species of powdery mildew fungi that cause disease on Arabidopsis has opened a new chapter in this research field. The great advantages of working with a model plant species have translated into remarkable progress in our understanding of these complex pathogens and their interaction with the plant host. Herein we summarize advances in the study of Arabidopsis-powdery mildew interactions and discuss their implications for the general field of plant pathology. We provide an overview of the life cycle of the pathogens on Arabidopsis and describe the structural and functional changes that occur during infection in the host and fungus in compatible and incompatible interactions, with special emphasis on defense signaling, resistance pathways, and compatibility factors. Finally, we discuss the future of powdery mildew research in anticipation of the sequencing of multiple powdery mildew genomes. The cumulative body of knowledge on powdery mildews of Arabidopsis provides a valuable tool for the study and understanding of disease associated with many other obligate biotrophic pathogen species.

A nonself recognition gene complex in Neurospora crassa.

Nonself recognition is exemplified in the fungal kingdom by the regulation of cell fusion events between genetically different individuals (heterokaryosis). The het-6 locus is one of approximately 10 loci that control heterokaryon incompatibility during vegetative growth of N. crassa. Previously, it was found that het-6-associated incompatibility in Oak Ridge (OR) strains involves two contiguous genes, het-6 and un-24. The OR allele of either gene causes "strong" incompatibility (cell death) when transformed into Panama (PA)-background strains. Several remarkable features of the locus include the nature of these incompatibility genes (het-6 is a member of a repetitive gene family and un-24 also encodes the large subunit of ribonucleotide reductase) and the observation that un-24 and het-6 are in severe linkage disequilibrium. Here, we identify "weak" (slow, aberrant growth) incompatibility activities by un-24PA and het-6PA when transformed separately into OR strains, whereas together they exhibit an additive, strong effect. We synthesized strains with the new allelic combinations un-24PA het-6OR and un-24OR het-6PA, which are not found in nature. These strains grow normally and have distinct nonself recognition capabilities but may have reduced fitness. Comparing the Oak Ridge and Panama het-6 regions revealed a paracentric inversion, the architecture of which provides insights into the evolution of the un-24-het-6 gene complex.

On the independence of barrage formation and heterokaryon incompatibility in Neurospora crassa.

A barrage is a line or zone of demarcation that may develop at the interface where genetically different fungi meet. Barrage formation represents a type of nonself recognition that has often been attributed to the heterokaryon incompatibility system, which limits the co-occurrence of genetically different nuclei in the same cytoplasm during the asexual phase of the life cycle. While the genetic basis of the heterokaryon incompatibility system is well characterized in Neurospora crassa, barrage formation has not been thoroughly investigated. In addition to the previously described Standard Mating Reaction barrage, we identified at least three types of barrage in N. crassa; dark line, clear zone, and raised aggregate of hyphae. Barrage formation in N. crassa was evident only when paired mycelia were genetically different and only when confrontations were carried out on low nutrient growth media. Barrages were observed to occur in some cases between strains that were identical at all major heterokaryon incompatibility (het) loci and the mating-type locus, mat, which acts as a heterokaryon incompatibility locus during the vegetative phase of N. crassa. We also found examples where barrages did not form between strains that had genetic differences at het-6, het-c, and/or mat. Taken together, these results suggest that the genetic control of barrage formation in N. crassa can operate independently from that of heterokaryon incompatibility and mating type. Surprisingly, barrages were not observed to form when wild-collected strains of N. crassa were paired. However, an increase in the frequency of pairings that produced barrages was observed among strains obtained by back-crossing wild strains to laboratory strains, or through successive rounds of inbreeding of wild-derived strains, suggesting the presence in wild strains of genes that suppress barrage.