PubMed Health⌕ Search

Biomedical subjects

T Musso

Publications and source records attributed to T Musso.

At least 19 recordsLinked to original sources
PubMed2005

In vitro and in vivo immune stimulating effects of a new standardized Echinacea angustifolia root extract (Polinacea).

Polinacea is a new standardized hydroethanolic extract obtained from Echinacea angustifolia roots containing echinacoside (>4%), the high molecular weight polysaccharide IDN 5405 (>5%) and a isobutylamide fraction (<0.1%). For in vitro tests, a bacterial lipopolysaccharide-free (LPS-free) Polinacea has been prepared in order to avoid non-specific responses of immunocompetent cells. LPS-free Polinacea enhanced the immune functions as highlighted by the proliferation rate and gamma-interferon production in murine T-lymphocyte cell cultures stimulated by anti-CD3. LPS-free Polinacea did not have a direct role on macrophage response as measured in the nitric oxide production test using the J774 macrophage cells line. In vivo, Polinacea showed an immune stimulating activity by reducing the Candida albicans induced mortality both in normal and in cyclosporin A-treated mice.

Animals↗
PubMed2003

B19 virus infection in renal transplant recipients.

BACKGROUND: B19 virus infection with persistent anaemia has been reported in organ transplant recipients. Detection of B19 virus DNA in serum is the best direct marker of active infection. OBJECTIVE: The present study evaluated the incidence and clinical role of active B19 virus infection in renal transplant recipients presenting with anaemia. STUDY DESIGN: Forty-eight such recipients were investigated by nested PCR on serum samples. The controls were 21 recipients without anaemia. Active HCMV infection was also investigated as a marker of high immunosuppression. RESULTS AND CONCLUSIONS: In 11/48 (23%) patients B19 virus DNA was demonstrated in serum versus only 1/21 (5%) of the controls. Ten of these 11 patients had already been seropositive at transplantation and active infection occurred in eight of them during the first 3 months after transplantation. The remaining patient experienced a primary infection 9 months after transplantation. Eight (73%) of these 11 patients displayed a concomitant HCMV infection and four (36%) showed increasing serum creatinine levels but none developed glomerulopathy; 3/11 (27%) recovered spontaneously from anaemia whereas 8/11 (73%) needed therapy. In conclusion, the relatively high occurrence (23%) of B19 virus infection in patients presenting with anaemia, suggests that it should be considered in the differential diagnosis of persistent anaemia in renal transplant recipients. Presence of the viral DNA should be assessed early from transplantation and the viral load should be monitored to follow persistent infection and better understand the relation between active infection and occurrence of anaemia, and to assess the efficacy of IVIG therapy and/or immunosuppression reduction in clearing the virus.

Anemia↗
PubMed2001

Interaction of Bartonella henselae with the murine macrophage cell line J774: infection and proinflammatory response.

Bartonella henselae is the causative agent of cat scratch disease (CSD), a self-limiting condition characterized by a subacute regional lymphadenopathy that may develop into disseminated bartonellosis in immunocompromised subjects. Mice experimentally infected with B. henselae display typical liver and spleen granulomas rich in T cells and macrophages. So far there are no data on the interaction between bartonellae and macrophages. In order to clarify this topic, we investigated the interaction of B. henselae with J774, a mouse macrophage cell line. Analysis of bacterial uptake by functional assays and transmission electron microscopy indicates that bartonellae can enter and survive inside J774. Entry occurred within 30 min postinfection and reached a plateau at 160 min. Infection of J774 was followed by a dose-dependent release of the proinflammatory cytokines tumor necrosis factor alpha, interleukin 1beta (IL-1beta), and IL-6. Bartonellae persisted intracellularly without loss of viability for at least 8 h, and their number slightly decreased 24 h postinfection. Gamma interferon (IFN-gamma) treatment of J774 significantly decreased the number of recoverable bacteria at 8 and 24 h. This enhancement of macrophage bactericidal activity was associated with nitric oxide (NO) release and was prevented by the addition of the competitive inhibitor of NO synthesis N(G)-monomethyl L-arginine. These findings suggest that IFN-gamma-mediated activation of macrophages may be important for the clearing of B. henselae infection and that anti-B. henselae microbicidal activity of IFN-gamma-activated macrophages is mediated to a large extent by NO production.

Animals↗
PubMed2001

CD38 expression and functional activities are up-regulated by IFN-gamma on human monocytes and monocytic cell lines.

Human CD38, a surface molecule expressed by immature and activated T and B lymphocytes, has been characterized as a molecule transducing activation and proliferation signals, and intervening in adhesion to endothelium via its ligand CD31. CD38 is also a complex ectoenzyme featuring ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities, leading to the synthesis and degradation of cADPR, a Ca+-mobilizing agent. We investigated the effects of monocyte-activating stimuli (IFN-gamma, IL-2, LPS, TNF-alpha, and GM-CSF) on the expression and function of CD38, starting from the observation that human monocytes and the derived lines U937, THP-1, and Mono-Mac-6 bear the molecule on their surface. Our results indicate that IFN-gamma is a strong up-modulator of CD38, and IL-2 increases its expression only modestly. LPS, TNF-alpha, and GM-CSF had no detectable effects. Treatment with IFN-gamma produced a dose- and time-dependent up-regulation of CD38 in monocytes and monocytic lines, which was paralleled by increased ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities. Furthermore, CD38 ligation by specific MoAb reduced the IFN-gamma-dependent enhancement of monocyte-dynamic adhesion to endothelial monolayers. These findings identify IFN-gamma as a modulator of monocytic CD38 expression and indicate that CD38 plays a specific role in the activation and adhesion processes performed by monocytes.

ADP-ribosyl Cyclase↗
PubMed2001

Quantitative PCR in EBV-infected renal transplant patients.

In this study we investigated the levels of Epstein Barr virus (EBV) DNA by quantitative polymerase chain reaction (Q-PCR) in serum, whole blood and peripheral blood mononuclear cells (PBMC) from anti-EA IgG seropositive or anti-EA IgG seronegative EBV infected renal transplant recipients. We compared serological data with the viral load to monitor the risk of developing post-transplant lymphoproliferative disorders (PTLD). All patients were asymptomatic and none of them developed PTLD at the time of the study. EBV DNA quantitation for each patient varied in whole blood and PBMC samples probably due to different numbers of mononuclear cells present in samples from which DNA was extracted (whole blood vs. purified PBMC). In 92% of the serum samples EBV DNA was undetectable probably due to absence of free genomes since the number of DNA copies detected in samples from whole blood and PBMC does not reach very high levels. The correlation between the presence of EA-antibody, considered serological evidence of EBV reactivation, and the viral load showed that 60% of EA-positive patients had quantifiable EBV DNA, whereas in 40% of EA-positive patients EBV DNA was undetectable, showing serological reactivity but no viral replication. Of the remaining EA-negative patients, EBV DNA could be detected in 71% of them, whereas 29% did not show EBV DNA, indicating no EBV replication. In conclusion, our results confirm that the presence of serum IgG anti-EA antibody is not a reliable marker of active EBV infection whereas the evaluation of the viral load in blood samples is a useful diagnostic tool to monitor and to better understand the course of EBV infection in immunocompromised renal transplant patients at risk of developing PTLD.

Adult↗
PubMed2000

Serum amyloid A is an activator of PMN antimicrobial functions: induction of degranulation, phagocytosis, and enhancement of anti-Candida activity.

Serum amyloid A (SAA) is a 12-kDa protein secreted in large amounts by liver cells during microbial infections or inflammatory diseases. We have recently reported that SAA induces chemotaxis of polymorphonuclear cells (PMN), monocytes, and T lymphocytes and stimulates their adhesion to endothelial monolayers. In this study, we investigated whether SAA regulates PMN antimicrobial activities. We found that recombinant SAA (rSAA), at concentrations comparable to serum levels attained during an acute phase response, is a potent activator of PMN. Stimulation of PMN by rSAA results in a rapid and transient increase of cytosolic calcium concentration and up-regulation of cell-surface expression of antigens involved in adhesion and microbial recognition such as CD11c and CD16. In addition, stimulation of PMN with rSAA increases secretion of lactoferrin, an antimicrobial protein that is contained in specific granules of PMN and enhances PMN phagocytic activity against heat-killed Candida albicans. Finally, activation of PMN with rSAA enhances their anti-Candida activity within 30 min of stimulation. These results suggest that SAA is involved in up-regulating PMN antimicrobial activities and that high circulating concentrations of SAA as seen in the acute phase response may constitute a potential host defense mechanism against fungal infections.

Acute-Phase Reaction↗
PubMed1999

Human monocytes constitutively express membrane-bound, biologically active, and interferon-gamma-upregulated interleukin-15.

Interleukin-15 (IL-15) is a potent regulator of T-, B-, and natural killer cell proliferation and displays unusually tight controls of secretion. Even though IL-15 mRNA is constitutively expressed in monocytes/macrophages and is upregulated by a variety of stimuli, evidence for IL-15 cytokine secretion is only found exceptionally, eg, conditions of pathological, chronic inflammation. This raises the possibility that monocytes express membrane-bound IL-15 rather than secrete it. The current study explores this hypothesis. We demonstrate here that biologically active IL-15 is indeed detectable in a constitutively expressed, membrane-bound form on normal human monocytes, as well as on monocytic cell lines (MONO-MAC-6, THP-1, and U937), but not on human T or B cells (MT4, M9, C5966, JURKAT, DAUDI, RAJI, and Epstein-Barr virus-immortalized B-cell clones). Furthermore, cell surface-bound IL-15 is upregulated upon interferon-gamma stimulation. Interestingly, monocyte/macrophage inhibitory cytokines such as IL-4 and IL-13 fail to downregulate both constitutive and induced cell-surface expression of IL-15. Membrane-bound IL-15 does not elute with acetate buffer or trypsin treatment, suggesting that it is an integral membrane protein and that it is not associated with the IL-15 receptor complex. Finally, membrane-bound IL-15 stimulates T lymphocytes to proliferate in vitro, indicating that it is biologically active. These findings enlist IL-15 in the fairly small family of cytokines for which the presence of a biologically active membrane-bound form has been demonstrated (eg, IL-1, tumor necrosis factor-alpha, and IL-10) and invites the speculation that most of the biological effects of IL-15 under physiological conditions are exerted by the cell surface-bound form.

Cells, Cultured↗
PubMed1999

Expression and role of IL-15 in post-burn hypertrophic scars.

Hypertrophic scarring is a skin disorder that occurs after wounding and thermal injury. There is accumulating evidence that immunologic processes such as infiltration of activated T lymphocytes and altered cytokine production may play a role in the formation of hypertrophic scars. Interleukin-15, a cytokine identified as a T cell growth factor, also acts as a chemoattractant for T cells and has pro-inflammatory properties. We investigated the expression and the role of this cytokine in hypertrophic scarring. IL-15 expression was compared in skin biopsies of hypertrophic scars (HS) both in active (AHS) and in remission (RHS) phases, in normotrophic scars (NTS) and in normal skin using reverse transcriptase-polymerase chain reaction and immunohistochemistry. IL-15 expression in HS was significantly higher than in NTS or normal skin. Furthermore, AHS expressed higher levels of IL-15 than RHS. Immunohistologic analysis of AHS samples showed strong IL-15 immunoreactivity in keratinocytes and Langerhans cells in the epidermis and in macrophages, fibroblasts, and dermal dendritic cells in the dermis. High levels of IL-15 expression in AHS correlated with abundant infiltration of activated CD3+ cells. Ex vivo experiments indicate that IL-15 can sustain the proliferative response of T cells derived from AHS but not from RHS and NTS. In addition, IL-15 prevents both cytokine deprivation and activation-induced apoptosis of T cells derived from AHS. Taken together, these results suggest that IL-15 can be involved in the recruitment, proliferation, and apoptosis inhibition of T cells in AHS. The findings that the evolution from an AHS to a RHS is associated with a decrease in IL15 expression, and with a loss of IL-15 responsiveness in ex vivo-cultured T cells, indicate that this cytokine plays an important role in the biology of pathologic scar formation.

Adolescent↗
PubMed1998

Interleukin-15 activates proinflammatory and antimicrobial functions in polymorphonuclear cells.

Interleukin-15 (IL-15) is a recently discovered cytokine produced by a wide range of different cell types including fibroblasts, keratinocytes, endothelial cells, and macrophages in response to lipopolysaccharide or microbial infection. This suggests that IL-15 may play a crucial role in the activation of phagocytic cells against pathogens. We studied polymorphonuclear leukocyte (PMN) activation by IL-15, evaluated as enhancement of PMN anti-Candida activity as well as IL-8 production, following stimulation with the cytokine. The PMN response to IL-15 depends on binding to the IL-15 receptor. Our experiments show that binding of a biotinylated human IL-15-immunoglobulin G2b IgG2b fusion protein was competed by the addition of human recombinant IL-15 (rIL-15) or of human rIL-2, suggesting that IL-15 binding to PMN might involve the IL-2Rbeta and IL-2Rgamma chains, which have been shown to be constitutively expressed by PMN. In addition, we show by reverse transcription-PCR and by flow cytometry with a specific anti-IL-15Ralpha chain monoclonal antibody that PMN express the IL-15Ralpha chain at the mRNA and protein levels. Incubation with IL-15 activated PMN to secrete the chemotactic factor IL-8, and the amount secreted was increased by costimulation with heat-inactivated Candida albicans. In addition, IL-15 primed the metabolic burst of PMN in response to formyl-methionyl-leucyl-phenylalanine but was not sufficient to trigger the respiratory burst or to increase the production of superoxide in PMN exposed to C. albicans. IL-15 also increased the ability of PMN to phagocytose heat-killed C. albicans organisms in a dose-dependent manner, without opsonization by antibodies or complement-derived products. In the same concentration range, IL-15 was as effective as gamma interferon (IFN-gamma) and IL-2 in increasing the C. albicans growth-inhibitory activity of PMN. Taken together, these results suggest that IL-15 is a potent stimulant of both proinflammatory and antifungal activities of PMN, activating several antimicrobial functions of PMN involved in the cellular response against C. albicans.

Candida albicans↗
PubMed1997

Interleukin-15 (IL-15) induces IL-8 and monocyte chemotactic protein 1 production in human monocytes.

Interleukin-15 (IL-15) is a recently characterized cytokine that shares many biological activities with IL-2 and interacts with the beta and gamma components of the IL-2 receptor. Unlike IL-2, which is secreted only by T cells, IL-15 is expressed preferentially by nonlymphoid tissues, epithelial, and fibroblast cell lines and by activated monocytes/macrophages. High concentrations of IL-15 have been shown in inflamed joints of rheumatoid arthritis patients, suggesting a role for IL-15 in inflammatory diseases where there is recruitment of leukocytes. Although monocytes have been shown to bind IL-15, its effects on these cells are not defined. In this report we show that supernatants of monocytes treated with IL-15-contained chemotactic activity for neutrophils and monocytes which was neutralized by anti-IL-8 or by anti-monocyte chemotactic protein 1 (MCP-1) antibodies, respectively. Secretion of IL-8 and MCP-1 proteins is detectable by enzyme-linked immunosorbent assay as early as 6 hours after stimulation with IL-15. Production of the two chemokines is correlated with induction by IL-15 of mRNA expression in monocytes. In addition, IL-8 and MCP-1 induction by IL-15 is differently regulated by interferon-gamma (IFN-gamma) and IL-4. IFN-gamma inhibited IL-15-induced IL-8 secretion, but synergized with IL-15 in MCP-1 induction; whereas IL-4 inhibited both IL-8 and MCP-1 induction by IL-15. These results show that IL-15 can stimulate monocytes to produce chemokines that cause inflammatory cell accumulation. Thus, IL-15 locally produced at sites of inflammation may play a pivotal role in the regulation of the leukocyte infiltrate.

Cells, Cultured↗
PubMed1997

Functional requirement of the hypoxia-responsive element in the activation of the inducible nitric oxide synthase promoter by the iron chelator desferrioxamine.

We have previously reported that a 19-base pair element of the 5'-flanking region of the inducible nitric oxide synthase (iNOS) gene containing a sequence homology to a hypoxia-responsive enhancer (iNOS-HRE) mediates picolinic acid (PA)- or hypoxia-induced activation of the iNOS promoter in interferon-gamma (IFN-gamma)-treated murine macrophages. The iron chelator desferrioxamine (DFX) induces the activity of the human erythropoietin enhancer in Hep3B cells. We have investigated the influence of DFX on the activation of the iNOS promoter and iNOS gene expression in ANA-1 macrophages. We have found that DFX induced DNA-binding activity to the hypoxia-inducible factor 1 (HIF-1) consensus sequence of the iNOS promoter and activated the iNOS-HRE in murine macrophages. These activities of DFX were associated with a synergistic induction of iNOS mRNA expression and iNOS transcription in IFN-gamma-treated ANA-1 macrophages. Functional analysis of the 5'-flanking region of the iNOS gene demonstrated that IFN-gamma plus DFX activated the full-length iNOS promoter and that the iNOS-HRE was required for DFX-induced iNOS transcriptional activity. We also investigated the role of iron metabolism in the DFX- or PA-dependent induction of HIF-1 activity and iNOS expression. We demonstrate that addition of iron sulfate completely abolished DFX or PA induction of HIF-1 binding and iNOS-HRE activation and abrogated IFN-gamma plus either DFX- or PA-induced iNOS expression. These data establish that DFX is a co-stimulus for the transcriptional activation of the iNOS gene in IFN-gamma-treated macrophages, and they provide evidence that the iNOS-HRE is required for the DFX-dependent activation of the iNOS promoter. Furthermore, our results indicate that the iNOS-HRE is a regulatory element of the iNOS promoter responsive to iron chelation.

Animals↗
PubMed1997

Interleukin 6 gene-transfected mouse mammary adenocarcinoma: tumour cell growth and metastatic potential.

Cells from the spontaneous metastatic TSA mammary adenocarcinoma of BALB/C mouse were transfected with the murine (interleukin-6) IL6 gene. The clone (TSA-IL6) secreting the largest amount of IL6 displayed an in vitro increased growth rate compared with that of TSA cells transfected with the neomycin resistance gene only (TSA-neo). TSA-IL6 cell colonies consisted mainly of fusiform cells and TSA-neo colonies of polygonal cells. When subcutaneously (s.c.) injected in syngeneic mice, TSA-IL6 cells gave rise to tumours that grew significantly slower than TSA-neo cell tumours. Microscopically, TSA-IL6 tumours displayed a fascicular pattern of growth, associated with a very scanty macrophage infiltrate. S.c. TSA-IL6 tumours were significantly less metastatic than TSA-neo tumours. By contrast, following intravenous (i.v.) challenge, TSA-IL6 cells produced 5-7 times more lung metastases than TSA-neo cells. The i.v. TSA-IL6 cell lung metastases showed a marked macrophage infiltrate and a rich vascularization. The high in vitro TSA-IL6 cell growth rate is attributable to the IL6-induced production of growth factors, some of which possess heparin-binding properties, such as amphiregulin. The differences in vascularization and macrophage infiltrate may underlie the observed differences between s.c. TSA-IL6 tumour growth with low spontaneous metastatic potential and the widespread growth of i.v. metastasis.

Adenocarcinoma↗
PubMed1997

Activation of human immunodeficiency virus long terminal repeat by arachidonic acid.

Arachidonic acid is the precursor of highly reactive mediators, including prostaglandins and leukotrienes, and the most abundant n-6 polyunsaturated fatty acid in mammalian cell membranes. It is released from phospholipids upon many inflammatory stimuli. In this study, a chloramphenicol acyltransferase reporter gene, under control of the human immunodeficiency virus-1 long terminal repeat, was strongly induced upon treating human promonocytes with arachidonic acid. The n-3 fatty acid eicosapentenoic, found in abundance in fish oil, had no effect. HIV-1 long terminal repeat activation by arachidonic acid was suppressed by inhibitors of both lipoxygenase and cyclooxygenase pathways, suggesting that metabolites, rather than arachidonic acid itself, mediated the stimulatory effect. This is the first report linking HIV-1 expression to the metabolism of arachidonic acid.

Analysis of Variance↗
PubMed1997

The Csk-like proteins Lsk, Hyl, and Matk represent the same Csk homologous kinase (Chk) and are regulated by stem cell factor in the megakaryoblastic cell line MO7e.

Recently, the cDNAs for Lsk, Matk and Hyl, three Csk-related protein tyrosine kinases, have been cloned. We have examined the relationship of Lsk, Matk and Hyl, and found that the gene for each of these proteins is localized to the same region of human chromosome 19. Further, the proteins encoded by Lsk and Matk cDNAs are immunologically similar. These data strongly suggest that Lsk, Hyl and Matk are the same gene product. Previous reports demonstrating expression of Hyl and Matk in hematopoietic lineages led us to investigate the regulation of Lsk expression in response to stem cell factor (SCF) and granulocyte-macrophage colony stimulating factor (GM-CSF) in M07e, a human leukemic cell line. Induction of Lsk/Hyl/Matk protein and mRNA was observed after treatment with SCF but not with GM-CSF. GM-CSF and IL-3, potent mitogens, had no effect on Lsk/Hyl/Matk expression. In contrast, PMA induced Lsk/Hyl/Matk but did not stimulate proliferation. Therefore, induction of Lsk/ Hyl/Matk does not correlate with the capacity to stimulate proliferation. None of the stimuli examined increased Csk protein or mRNA expression. These data demonstrate differential regulation of Csk family members by cytokines and suggest a role for Lsk/ Hyl/Matk in responses mediated by SCF and PMA. Further, our data demonstrate that, as has been seen in blood monocytes, cytokine driven translational control of Lsk/Hyl/ Matk is likely a critical mode of regulation. Lastly, since our studies strongly suggest that the Lsk, Hyl and Matk kinases are related and regulated distinctly from Csk, we and several of the original authors have agreed to rename this kinase the Csk homologous kinase (Chk).

Blotting, Western↗
PubMed1996

Nuclear factor kB is activated by arachidonic acid but not by eicosapentaenoic acid.

The omega-6 arachidonic acid supplementation of the human promonocytic cell line U937 strongly stimulates the nuclear translocation of the transcription factor NF-kB. Inhibitors of arachidonate oxidative metabolism prevent NF-kB activation, indirectly indicating a role for prostaglandin and leukotriene metabolites in the genesis of this phenomenon. Of note, omega-3 eicosapentaenoic acid does not exert any effect on NF-kB DNA binding. In subsequent experiments, prostaglandin E2 consistently showed the ability to activate NF-kB in U937 promonocytic cells, as well as in J774 macrophages. NF-kB activation by arachidonate, together with the lack of effect by eicosapentaenoic acid, suggests a way to modulate the expression of certain genes by means of a suitable dietary n-6/n-3 fatty acid ratio.

Arachidonic Acid↗
PubMed1996

Leishmania major: infection of human monocytes induces expression of IL-8 and MCAF.

Leishmania major, the causative agent of cutaneous leishmaniasis, is an intracellular parasite of monocytic cells. Leishmania lesions are characterized by recruitment of neutrophils, eosinophils, and blood monocytes. To clarify the mechanism of this cellular influx we examined the expression of IL-8 and MCAF, cytokines chemotactic for neutrophils and monocytes, respectively, in human monocytes infected by L. major. Supernatants of monocytes infected with L. major had chemotactic activity for neutrophils and monocytes that was neutralized by anti-IL-8 and anti-MCAF antibodies. Both IL-8 and MCAF mRNAs were induced within 1 hr of infection. Furthermore we showed that infection of monocytes with L. major induces IL-8 and MCAF but not the proinflammatory cytokines IL-1 beta and TNF alpha. These data suggest that the expression of chemokines may contribute to the cellular recruitment in Leishmania lesions.

Animals↗
PubMed1996

Pseudomonas aeruginosa clinical isolates: serotypes, resistance phenotypes and plasmid profiles.

78 Pseudomonas aeruginosa strains were isolated from the respiratory tract of 56 patients, 15 of which were affected by cystic fibrosis (CF). The epidemiological typing scheme was based on serotyping, antibiotic resistance pattern and plasmid DNA profile. All strains (except 2 mucoid strains) were typed using a rapid slide O-agglutination technique. Most common serotypes in both group were 0:1, 0:10 and 0:6. Moreover we observed a correlation among 0:12 serotype and CF patients. Plasmid DNA analysis showed that 45.2% (on average) of strains isolated from patients with and w/o CF harboured 1-3 plasmids ranging in size from 1 to 15 Md. Plasmid prevalence was higher in strains isolated from CF patients in specimens collected after antibiotic therapy. A correlation was found between 1 and 1.9 Md plasmids and resistance to aminoglycosides. Our results indicate that the analysis of antibiotic resistance phenotypes combined with plasmid analysis may be useful, in association to serotyping, to characterize the circulation of P. aeruginosa strains and the spread of resistance in these bacteria.

Cystic Fibrosis↗