%PDF-1.4
%
15 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
8 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
3 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
16 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
19 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
21 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
11 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
14 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
20 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
13 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
6 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
9 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
1 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
18 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
10 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
7 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
4 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
12 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
17 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
5 0 obj
<>>>/BBox[0 0 584.96 782.99]/Length 150>>stream
x5;0 Z$NG=A.x{Ca;{L8=@BeJ^($WkOmˊBNsV)=Bf
%
SoRA?$Z$v.XuBMoZ~#?.p
endstream
endobj
23 0 obj
<>stream
Rothia from the Human Nose Inhibit Moraxella catarrhalis Colonization with a Secreted Peptidoglycan Endopeptidase
10.1128/mbio.00464-23
Reed M. Stubbendieck
Eishika Dissanayake
Peter M. Burnham
Susan E. Zelasko
Mia I. Temkin
Sydney S. Wisdorf
Rose F. Vrtis
James E. Gern
Cameron R. Currie
Research Article
Research Article
asthma
acute otitis media
Moraxella catarrhalis
nasal microbiome
peptidoglycan endopeptidase
Rothia aeria
Rothia dentocariosa
Rothia mucilaginosa
Rothia
asthma
American Society for Microbiology
Stubbendieck et al.
Copyright © 2023 Stubbendieck et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
20230403
2023
ABSTRACT
Moraxella catarrhalis is found almost exclusively within the human respiratory tract. This pathobiont is associated with ear infections and the development of respiratory illnesses, including allergies and asthma. Given the limited ecological distribution of M. catarrhalis, we hypothesized that we could leverage the nasal microbiomes of healthy children without M. catarrhalis to identify bacteria that may represent potential sources of therapeutics. Rothia was more abundant in the noses of healthy children compared to children with cold symptoms and M. catarrhalis. We cultured Rothia from nasal samples and determined that most isolates of Rothia dentocariosa and “Rothia similmucilaginosa” were able to fully inhibit the growth of M. catarrhalis in vitro, whereas isolates of Rothia aeria varied in their ability to inhibit M. catarrhalis. Using comparative genomics and proteomics, we identified a putative peptidoglycan hydrolase called secreted antigen A (SagA). This protein was present at higher relative abundance in the secreted proteomes of R. dentocariosa and R. similmucilaginosa than in those from non-inhibitory R. aeria, suggesting that it may be involved in M. catarrhalis inhibition. We produced SagA from R. similmucilaginosa in Escherichia coli and confirmed its ability to degrade M. catarrhalis peptidoglycan and inhibit its growth. We then demonstrated that R. aeria and R. similmucilaginosa reduced M. catarrhalis levels in an air-liquid interface culture model of the respiratory epithelium. Together, our results suggest that Rothia restricts M. catarrhalis colonization of the human respiratory tract in vivo.
IMPORTANCE Moraxella catarrhalis is a pathobiont of the respiratory tract, responsible for ear infections in children and wheezing illnesses in children and adults with chronic respiratory diseases. Detection of M. catarrhalis during wheezing episodes in early life is associated with the development of persistent asthma. There are currently no effective vaccines for M. catarrhalis, and most clinical isolates are resistant to the commonly prescribed antibiotics amoxicillin and penicillin. Given the limited niche of M. catarrhalis, we hypothesized that other nasal bacteria have evolved mechanisms to compete against M. catarrhalis. We found that Rothia are associated with the nasal microbiomes of healthy children without Moraxella. Next, we demonstrated that Rothia inhibit M. catarrhalis in vitro and on airway cells. We identified an enzyme produced by Rothia called SagA that degrades M. catarrhalis peptidoglycan and inhibits its growth. We suggest that Rothia or SagA could be developed as highly specific therapeutics against M. catarrhalis.
20230224
20230227
2150-7511
Adobe LiveCycle PDF Generator; modified using iText® 5.5.13.2 ©2000-2020 iText Group NV (AGPL-version)2023-04-26T20:54:16-07:00
endstream
endobj
24 0 obj
<>stream
x+ |
endstream
endobj
25 0 obj
<>stream
xS**T0T0 Bih \
endstream
endobj
26 0 obj
<>stream
x+ |
endstream
endobj
27 0 obj
<>stream
xS**T0T0 Bi yn)
endstream
endobj
28 0 obj
<>stream
x+ |
endstream
endobj
29 0 obj
<>stream
xS**T0T0 Bi yS&
endstream
endobj
30 0 obj
<>stream
x+ |
endstream
endobj
31 0 obj
<>stream
xS**T0T0 Bi y,
endstream
endobj
32 0 obj
<>stream
x+ |
endstream
endobj
33 0 obj
<>stream
xS**T0T0 Bi yA$
endstream
endobj
34 0 obj
<>stream
x+ |
endstream
endobj
35 0 obj
<>stream
xS**T0T0 Bih W
endstream
endobj
36 0 obj
<>stream
x+ |
endstream
endobj
37 0 obj
<>stream
xS**T0T0 Bih uU
endstream
endobj
38 0 obj
<>stream
x+ |
endstream
endobj
39 0 obj
<>stream
xS**T0T0 Bih Z
endstream
endobj
40 0 obj
<>stream
x+ |
endstream
endobj
41 0 obj
<>stream
xS**T0T0 Bih ~V
endstream
endobj
42 0 obj
<>stream
x+ |
endstream
endobj
43 0 obj
<>stream
xS**T0T0 Bih [
endstream
endobj
44 0 obj
<>stream
x+ |
endstream
endobj
45 0 obj
<>stream
xS**T0T0 Bih ]
endstream
endobj
46 0 obj
<>stream
x+ |
endstream
endobj
47 0 obj
<>stream
xS**T0T0 Bih Y
endstream
endobj
48 0 obj
<>stream
x+ |
endstream
endobj
49 0 obj
<>stream
xS**T0T0 Bi ye(
endstream
endobj
50 0 obj
<>stream
x+ |
endstream
endobj
51 0 obj
<>stream
xS**T0T0 Bi yw*
endstream
endobj
52 0 obj
<>stream
x+ |
endstream
endobj
53 0 obj
<>stream
xS**T0T0 Bi y8#
endstream
endobj
54 0 obj
<>stream
x+ |
endstream
endobj
55 0 obj
<>stream
xS**T0T0 Bi yJ%
endstream
endobj
56 0 obj
<>stream
x+ |
endstream
endobj
57 0 obj
<>stream
xS**T0T0 Bi y\'
endstream
endobj
58 0 obj
<>stream
x+ |
endstream
endobj
59 0 obj
<>stream
xS**T0T0 Bi y+
endstream
endobj
60 0 obj
<>stream
x+ |
endstream
endobj
61 0 obj
<>stream
xS**T0T0 Bih X
endstream
endobj
62 0 obj
<>stream
x+ |
endstream
endobj
63 0 obj
<>stream
xS**T0T0 Bih lT
endstream
endobj
65 0 obj
<>stream
HWn+t1D6s<>|R@UQ*ΔHȒz7<:^D$ki0bfFFE?O?[{{t"ޖ?+ʲ
UOmyI|ތ7o{s3)EQZHzkn2ufoyvCcݞu,lcl[Ygl,@?&l1~%>MEwNYZш*m؆F=m#m8)d%=$BOKwckh]u<': m>6)pݥ
1`!*ӟ#pg~1Αj>iDH/%o儰*o
| M>S߽4u49w<_& VA6w4r#)A6oA("1UQ}I[Ы?bsu0G&xr{M cD׳iki9}5ʗk3 y'ѯla][ѧI;OhQz89]eCKgŗ?
Hs+F4PcCHV9Xr}cE]u+PL(a+{)R_h⪮mE7/of_$33kWRYlߖ=>~bHH҅պlNiac092҆|+zJoOd/NHgr@^NcYj0%+Gf0Ltv:qC-M\/s8.#dAU:= i#-دQC~;+`^8vM)8^&9x@9!66gnhZ!rR8rʆSUvQ8Lԏ
F 5"rWb"_TI^
|ҢfI\!y\tNĔ1P6(X]?N+j`m}}'xV{KH- b~da3ci=[G&LX3Q¥5G>C.+|1#jM%99bRU_H
GH ReC
Qu^MKaN$H\!%2-vkm}j87l3x gq3
j^t0:WDѐia .&o9 GmHlW
)?@5E'#sGSq5cbvOVlewR=%yzREZὑ$Mi_f4d~M9_QheA.'HꑷZ. klM1"?S !!?i)!=ʃ''lE!==HS~vؾ9aSU6)}g"H-QW:(ۉU,|yay-V0O0E7ѥ94!2ۋ*]C%ETpi߃ ,ПpHoA{AJa 5h@xn|b8|4Ą|&n/p@|u;*[$NC7Ⱦ+E(Z%d$NI=I9ExB0\i S"A;,19Z"Gl.yj/\鉓PwC,0 JIE^mӌ+4Zr[o1v((U[/` 6ksE!IA}e1N/%F; @6IbCjO
"LWIp.I'#=4pꥉ
UJ`FI}(V5Nm9J@Swa-93iD_: F&QɭD lFY?D~968j6ELʮ##F+%}tG&ҊT F0 L{7gb!=̣8-dG._a>\kˌ}NxW
63L˰0TK:YBG/y>a|70TW-no="?}lb4_{Yq,| NvNz5ʸJDR?/Be}K~=!ċYuyf_a
68/:"IsC6rrMy>.i{dbT*>I:Ǘi3m6T2{6aEE%w#}k&]wM(_pCHq=C
3PϢP'!Fx4=)#SI/V}:y(%TD^ $u?@gx*&*]gӾUe"lT*_t4(AO /^#~ޡg zXSxީ9B;RʕJl'lȯ#yRsFyRvxl6J2Kѡ8i*xM!鑇NXyb,}^#h,Fi6j)!z\d=]suL bf͒{,rLFnhJzx$3CB:<yzeҹLd:ݞ)%OIpvg[bzaCDh~.1U" itP+